Jason G Umans

Publications (55)282.94 Total impact

• Article: Association of Functional Polymorphism rs2231142 (Q141K) in the ABCG2 Gene With Serum Uric Acid and Gout in 4 US Populations: The PAGE Study.

  Lili Zhang, Kylee L Spencer, V Saroja Voruganti, Neal W Jorgensen, Myriam Fornage, Lyle G Best, Kristin D Brown-Gentry, Shelley A Cole, Dana C Crawford, Ewa Deelman, [......], Kimberly R Glenn, Gerardo Heiss, Nancy S Jenny, Anna Kottgen, Qiong Li, Kiang Liu, Tara C Matise, Kari E North, Jason G Umans, W H Linda Kao
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  ABSTRACT: A loss-of-function mutation (Q141K, rs2231142) in the ATP-binding cassette, subfamily G, member 2 gene (ABCG2) has been shown to be associated with serum uric acid levels and gout in Asians, Europeans, and European and African Americans; however, less is known about these associations in other populations. Rs2231142 was genotyped in 22,734 European Americans, 9,720 African Americans, 3,849 Mexican Americans, and 3,550 American Indians in the Population Architecture using Genomics and Epidemiology (PAGE) Study (2008-2012). Rs2231142 was significantly associated with serum uric acid levels (P = 2.37 × 10(-67), P = 3.98 × 10(-5), P = 6.97 × 10(-9), and P = 5.33 × 10(-4) in European Americans, African Americans, Mexican Americans, and American Indians, respectively) and gout (P = 2.83 × 10(-10), P = 0.01, and P = 0.01 in European Americans, African Americans, and Mexican Americans, respectively). Overall, the T allele was associated with a 0.24-mg/dL increase in serum uric acid level (P = 1.37 × 10(-80)) and a 1.75-fold increase in the odds of gout (P = 1.09 × 10(-12)). The association between rs2231142 and serum uric acid was significantly stronger in men, postmenopausal women, and hormone therapy users compared with their counterparts. The association with gout was also significantly stronger in men than in women. These results highlight a possible role of sex hormones in the regulation of ABCG2 urate transporter and its potential implications for the prevention, diagnosis, and treatment of hyperuricemia and gout.
  American journal of epidemiology 04/2013; · 5.59 Impact Factor
• Article: Cadmium Exposure and Incident Cardiovascular Disease.

  Maria Tellez-Plaza, Eliseo Guallar, Barbara V Howard, Jason G Umans, Kevin A Francesconi, Walter Goessler, Ellen K Silbergeld, Richard B Devereux, Ana Navas-Acien
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  ABSTRACT: BACKGROUND:: Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort. METHODS:: We conducted a prospective cohort study of 3348 American Indian adults 45-74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989-1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008. RESULTS:: The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval [CI] = 0.92-0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21-1.70) and 1.34 for coronary heart disease mortality (1.10-1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11-1.38), 1.22 (1.08-1.38), 1.75 (1.17-2.59), and 1.39 (1.01-1.94), respectively. The associations were similar in most study subgroups, including never-smokers. CONCLUSIONS:: Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor.
  Epidemiology (Cambridge, Mass.) 03/2013; · 5.51 Impact Factor
• Article: Heritability and Preliminary Genome-Wide Linkage Analysis of Arsenic Metabolites in Urine.

  Maria Tellez-Plaza, Matthew O Gribble, V Saroja Voruganti, Kevin A Francesconi, Walter Goessler, Jason G Umans, Ellen K Silbergeld, Eliseo Guallar, Nora Franceschini, Kari E North, Wen H Kao, Jean W Maccluer, Shelley A Cole, Ana Navas-Acien
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  ABSTRACT: BACKGROUND: Arsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might play a role in arsenic metabolism and excretion. OBJECTIVE: To evaluate genetic determinants of urine arsenic metabolites in American Indian adults from the Strong Heart Study (SHS). METHODS: We evaluated heritability of urine arsenic metabolites [% inorganic arsenic (iAs), % monomethylarsonate (MMA), and % dimethylarsinate (DMA)] in 2,907 SHS participants with urine arsenic measurements and at least one relative within the cohort. We conducted a preliminary linkage analysis in a subset of 487 participants with available genotypes on ~400 short tandem repeat markers using a general pedigree variance component approach for localizing quantitative trait loci (QTL). RESULTS: The median (interquartile range) for %iAs, %MMA and %DMA were 7.7% (5.4, 10.7%), 13.6% (10.5, 17.1%) and 78.4% (72.5, 83.1%), respectively. The estimated heritability was 53% for %iAs, 50% for %MMA and 59% for %DMA. After adjustment for sex, age, smoking, body mass index, alcohol, region and total urine arsenic concentrations, LOD scores indicated suggestive evidence for genetic linkage with QTLs influencing urine arsenic metabolites on chromosomes 9 (LOD=2.05 for % iAs and 2.10 for % MMA), 5 (LOD=2.03 for % iAs) and 11 (LOD=1.94 for %iAs). A peak for % DMA on chromosome 10 within 2 megabases of AS3MT had an LOD=1.80. CONCLUSIONS: This population-based family study in American Indian communities supports a genetic contribution to variation in the distribution of arsenic metabolites in urine, and potentially the involvement of genes beyond AS3MT.
  Environmental Health Perspectives 01/2013; · 7.04 Impact Factor
• Article: Perspectives on the proposed gestational diabetes mellitus diagnostic criteria.

  Oded Langer, Jason G Umans, Menachem Miodovnik
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  ABSTRACT: To date, The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) have not been analyzed systematically for medical, social, and economic ramifications if used in substitution for the current GDM diagnostic criteria. The IADPSG dependence on expert opinion and consensus rather than on rigorously obtained outcome measures is concerning given the dramatic changes in clinical intervention and medical-resource reallocation that would follow their wide adoption. This commentary attempts to highlight needed research as well as the key knowledge gaps that should prevent adoption of the revised criteria until their effect on perinatal outcomes and health care costs is determined. In light of the overall, ethnic, and regional variation in GDM prevalence and the demands of increased GDM diagnosis on clinical resources, it may not be realistic and practical to impose universal strategies and standards for diagnosis. The newly proposed criteria may affect medical care negatively, unnecessarily stigmatize patients with a "sick label," and adversely affect health care costs without ensuring the desired improvements in maternal and neonatal outcomes. This commentary serves as a caution to not promote a new endeavor until it has been compared rigorously with current practice and its implications are understood fully.
  Obstetrics and Gynecology 01/2013; 121(1):177-82. · 4.73 Impact Factor
• Article: Urine Arsenic and Prevalent Albuminuria: Evidence From a Population-Based Study.

  Laura Y Zheng, Jason G Umans, Maria Tellez-Plaza, Fawn Yeh, Kevin A Francesconi, Walter Goessler, Ellen K Silbergeld, Eliseo Guallar, Barbara V Howard, Virginia M Weaver, Ana Navas-Acien
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  ABSTRACT: BACKGROUND: Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota. STUDY DESIGN: Cross-sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements. PREDICTOR: Urine arsenic. OUTCOMES: Urine albumin-creatinine ratio and albuminuria status. MEASUREMENTS: Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry. RESULTS: The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) μg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria. LIMITATIONS: The cross-sectional design cannot rule out reverse causation. CONCLUSIONS: Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.
  American Journal of Kidney Diseases 11/2012; · 5.43 Impact Factor
• Article: Arsenic Exposure, Diabetes Prevalence, and Diabetes Control in the Strong Heart Study.

  Matthew O Gribble, Barbara V Howard, Jason G Umans, Nawar M Shara, Kevin A Francesconi, Walter Goessler, Ciprian M Crainiceanu, Ellen K Silbergeld, Eliseo Guallar, Ana Navas-Acien
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  ABSTRACT: This study evaluated the association of arsenic exposure, as measured in urine, with diabetes prevalence, glycated hemoglobin, and insulin resistance in American Indian adults from Arizona, Oklahoma, and North and South Dakota (1989-1991). We studied 3,925 men and women 45-74 years of age with available urine arsenic measures. Diabetes was defined as a fasting glucose level of 126 mg/dL or higher, a 2-hour glucose level of 200 mg/dL or higher, a hemoglobin A1c (HbA1c) of 6.5% or higher, or diabetes treatment. Median urine arsenic concentration was 14.1 µg/L (interquartile range, 7.9-24.2). Diabetes prevalence was 49.4%. After adjustment for sociodemographic factors, diabetes risk factors, and urine creatinine, the prevalence ratio of diabetes comparing the 75th versus 25th percentiles of total arsenic concentrations was 1.14 (95% confidence interval: 1.08, 1.21). The association between arsenic and diabetes was restricted to participants with poor diabetes control (HbA1c ≥8%). Arsenic was positively associated with HbA1c levels in participants with diabetes. Arsenic was not associated with HbA1c or with insulin resistance (assessed by homeostatic model assessment to quantify insulin resistance) in participants without diabetes. Urine arsenic was associated with diabetes control in a population from rural communities in the United States with a high burden of diabetes. Prospective studies that evaluate the direction of the relation between poor diabetes control and arsenic exposure are needed.
  American journal of epidemiology 10/2012; · 5.59 Impact Factor
• Article: The proposed GDM diagnostic criteria: A difference, to be a difference, must make a difference.

  Oded Langer, Jason G Umans, Menachem Miodovnik
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  ABSTRACT: Abstract The new criteria for diagnosis of gestational diabetes mellitus proposed by the International Diabetes in Pregnancy Consensus group (IADPSG) transports back the controversy and the lack of agreement to the frontlines. The recommended criteria are based on results of the observational hyperglycemia and adverse pregnancy outcome study (HAPO). These criteria will increase the frequency of gestational diabetes diagnosis by 2-8 fold, depending upon ethnicity, and prevalence of obesity. Do the costs and implied resources justify using the proposed endpoints that will define pregnancy outcome and severity especially when the appropriate outcomes and odds ratio used to define the diagnosis are questionable? Furthermore, due to the large disparity around the globe in relation to the prevalence of GDM raises the question if single diagnostic criteria can be made to fit all?!? The current review analyzes the risks, costs and benefits that may influence the rate of GDM in relation to the worldwide prevalence.
  The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2012; · 1.36 Impact Factor
• Article: Estimated GFR and Incident Cardiovascular Disease Events in American Indians: The Strong Heart Study.

  Nawar M Shara, Hong Wang, Mihriye Mete, Yaman Rai Al-Balha, Nameer Azalddin, Elisa T Lee, Nora Franceschini, Stacey E Jolly, Barbara V Howard, Jason G Umans
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  ABSTRACT: In populations with high prevalences of diabetes and obesity, estimating glomerular filtration rate (GFR) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation may predict cardiovascular disease (CVD) risk better than by using the Modification of Diet in Renal Disease (MDRD) Study equation. Longitudinal cohort study comparing the association of GFR estimated using either the CKD-EPI or MDRD Study equation with incident CVD outcomes. American Indians participating in the Strong Heart Study, a longitudinal population-based cohort with high prevalences of diabetes, CVD, and CKD. Estimated GFR (eGFR) predicted using the CKD-EPI and MDRD Study equations. Fatal and nonfatal cardiovascular events, consisting of coronary heart disease, stroke, and heart failure. The association between eGFR and outcomes was explored in Cox proportional hazards models adjusted for traditional risk factors and albuminuria; the net reclassification index and integrated discrimination improvement were determined for the CKD-EPI versus MDRD Study equations. In 4,549 participants, diabetes was present in 45%; CVD, in 7%; and stages 3-5 CKD, in 10%. During a median of 15 years, there were 1,280 cases of incident CVD, 929 cases of incident coronary heart disease, 305 cases of incident stroke, and 381 cases of incident heart failure. Reduced eGFR (<90 mL/min/1.73 m(2)) was associated with adverse events in most models. Compared with the MDRD Study equation, the CKD-EPI equation correctly reclassified 17.0% of 2,151 participants without incident CVD to a lower risk (higher eGFR) category and 1.3% (n = 28) were reclassified incorrectly to a higher risk (lower eGFR) category. Single measurements of eGFR and albuminuria at study visits. Although eGFR based on either equation had similar associations with incident CVD, coronary heart disease, stroke, and heart failure events, in those not having events, reclassification of participants to eGFR categories was superior using the CKD-EPI equation compared with the MDRD Study equation.
  American Journal of Kidney Diseases 07/2012; 60(5):795-803. · 5.43 Impact Factor
• Article: Differences in Risk Factors for Coronary Heart Disease among Diabetic and Nondiabetic Individuals from a Population with High Rates of Diabetes: The Strong Heart Study.

  Jiaqiong Xu, Elisa T Lee, Leif E Peterson, Richard B Devereux, Everett R Rhoades, Jason G Umans, Lyle G Best, William J Howard, Jaya Paranilam, Barbara V Howard
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  ABSTRACT: Context: Coronary heart disease (CHD) is the leading cause of death in the United States. Objective: This study compares differences in risk factors for CHD in diabetic vs. nondiabetic Strong Heart Study participants. Design: This was an observational study. Setting: The study was conducted at three centers in Arizona, Oklahoma, and North and South Dakota. Participants: Data were obtained from 3563 of 4549 American Indians free of cardiovascular disease at baseline. Intervention(s): CHD events were ascertained during follow-up. Main Outcome Measure: CHD events were classified using standardized criteria. Results: In diabetic and nondiabetic participants, 545 and 216 CHD events, respectively, were ascertained during follow-up (21,194 and 22,990 person-years); age- and sex-adjusted incidence rates of CHD were higher for the diabetic group (27.5 vs. 12.1 per 1,000 person-years). Risk factors for incident CHD common to both groups included older age, male sex, prehypertension or hypertension, and elevated low-density lipoprotein cholesterol. Risk factors specific to the diabetic group were lower high-density lipoprotein cholesterol, current smoking, macroalbuminuria, lower estimated glomerular filtration rate, use of diabetes medication, and longer duration of diabetes. Higher body mass index was a risk factor only for the nondiabetic group. The association of male sex and CHD was greater in those without diabetes than in those with diabetes. Conclusions: In addition to higher incidence rates of CHD events in persons with diabetes compared with those without, the two groups differed in CHD risk factors. These differences must be recognized in estimating CHD risk and managing risk factors.
  The Journal of clinical endocrinology and metabolism 07/2012; 97(10):3766-74. · 6.50 Impact Factor
• Article: Lipoprotein subfractions and dietary intake of n-3 fatty acid: the Genetics of Coronary Artery Disease in Alaska Natives study.

  Giovanni Annuzzi, Angela A Rivellese, Hong Wang, Lidia Patti, Olga Vaccaro, Gabriele Riccardi, Sven Oe Ebbesson, Anthony G Comuzzie, Jason G Umans, Barbara V Howard
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  ABSTRACT: Few studies have compared lipoprotein composition with dietary intake. The lipoprotein subfraction profile was evaluated in relation to diet in Alaska Eskimos at high cardiovascular risk but with a low frequency of hyperlipidemia and high intake of n-3 (omega-3) fatty acids. A population-based sample (n = 1214) from the Norton Sound Region of Alaska underwent a physical examination and blood sampling. Analyses were from 977 individuals who did not have diabetes or use lipid-lowering medications and had complete dietary information (food-frequency questionnaire) and a lipoprotein subfraction profile (nuclear magnetic resonance spectroscopy). After adjustment for age, BMI, total energy intake, and percentage of energy from fat, the intake of n-3 fatty acids was significantly associated with fewer large VLDLs (P = 0.022 in women, P = 0.064 in men), a smaller VLDL size (P = 0.018 and P = 0.036), more large HDLs (P = 0.179 and P = 0.021), and a larger HDL size (P = 0.004 and P = 0.001). After adjustment for carbohydrate and sugar intakes, large VLDLs (P = 0.042 and 0.018) and VLDL size (P = 0.011 and 0.025) remained negatively associated with n-3 fatty acid intake in women and men, and large HDLs (P = 0.067 and 0.005) and HDL size (P = 0.001 in both) remained positively associated with n-3 fatty acid intake in women and men. In addition, large LDLs (P = 0.040 and P = 0.025) were positively associated in both sexes, and LDL size (P = 0.006) showed a positive association in women. There were no significant relations with total LDL particles in either model. Dietary n-3 fatty acids, independent of the reciprocal changes in carbohydrate and sugar intakes, are associated with an overall favorable lipoprotein profile in terms of cardiovascular risk. Because there are no relations with total LDL particles, the benefit may be related to cardiovascular processes other than atherosclerosis.
  American Journal of Clinical Nutrition 05/2012; 95(6):1315-22. · 6.67 Impact Factor
• Article: The association of genetic variants of type 2 diabetes with kidney function.

  Nora Franceschini, Nawar M Shara, Hong Wang, V Saroja Voruganti, Sandy Laston, Karin Haack, Elisa T Lee, Lyle G Best, Jean W Maccluer, Barbara J Cochran, Thomas D Dyer, Barbara V Howard, Shelley A Cole, Kari E North, Jason G Umans
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  ABSTRACT: Type 2 diabetes is highly prevalent and is the major cause of progressive chronic kidney disease in American Indians. Genome-wide association studies identified several loci associated with diabetes but their impact on susceptibility to diabetic complications is unknown. We studied the association of 18 type 2 diabetes genome-wide association single-nucleotide polymorphisms (SNPs) with estimated glomerular filtration rate (eGFR; MDRD equation) and urine albumin-to-creatinine ratio in 6958 Strong Heart Study family and cohort participants. Center-specific residuals of eGFR and log urine albumin-to-creatinine ratio, obtained from linear regression models adjusted for age, sex, and body mass index, were regressed onto SNP dosage using variance component models in family data and linear regression in unrelated individuals. Estimates were then combined across centers. Four diabetic loci were associated with eGFR and one locus with urine albumin-to-creatinine ratio. A SNP in the WFS1 gene (rs10010131) was associated with higher eGFR in younger individuals and with increased albuminuria. SNPs in the FTO, KCNJ11, and TCF7L2 genes were associated with lower eGFR, but not albuminuria, and were not significant in prospective analyses. Our findings suggest a shared genetic risk for type 2 diabetes and its kidney complications, and a potential role for WFS1 in early-onset diabetic nephropathy in American Indian populations.
  Kidney International 04/2012; 82(2):220-5. · 6.61 Impact Factor
• Article: The association of the MYH9 gene and kidney outcomes in American Indians: the Strong Heart Family Study

  Nora Franceschini, V. Saroja Voruganti, Karin Haack, Laura Almasy, Sandy Laston, Harald H. H. Göring, Jason G. Umans, Elisa T. Lee, Lyle G. Best, Richard R. Fabsitz, Jean W. MacCluer, Barbara V. Howard, Kari E. North, Shelley A. Cole
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  ABSTRACT: Chronic kidney disease (CKD) is an important public health problem in American Indian populations. Recent research has identified associations of polymorphisms in the myosin heavy chain type II isoform A (MYH9) gene with hypertensive CKD in African-Americans. Whether these associations are also present among American Indian individuals is unknown. To evaluate the role of genetic polymorphisms in the MYH9 gene on kidney disease in American Indians, we genotyped 25 SNPs in the MYH9 gene region in 1,119 comparatively unrelated individuals. Four SNPs failed, and one SNP was monomorphic. We inferred haplotypes using seven SNPs within the region of the previously described E haplotype using Phase v2.1. We studied the association between 20 MYH9 SNPs with kidney function (estimated glomerular filtration rate, eGFR) and CKD (eGFR<60ml/min/1.73m2 or renal replacement therapy or kidney transplant) using age-, sex- and center-adjusted models and measured genotyped within the variance component models. MYH9 SNPs were not significantly associated with kidney traits in additive or recessive genetic adjusted models. MYH9 haplotypes were also not significantly associated with kidney outcomes. In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians.
  Human Genetics 04/2012; 127(3):295-301. · 5.07 Impact Factor
• Article: Genetic influence on variation in serum uric acid in American Indians: the strong heart family study

  V. Saroja Voruganti, Harald H. H. Göring, Amy Mottl, Nora Franceschini, Karin Haack, Sandra Laston, Laura Almasy, Richard R. Fabsitz, Elisa T. Lee, Lyle G. Best, Richard B. Devereux, Barbara V. Howard, Jean W. MacCluer, Anthony G. Comuzzie, Jason G. Umans, Shelley A. Cole
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  ABSTRACT: Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age×sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean±SD serum uric acid for all individuals was 5.14±1.5mg/dl. Serum uric acid was found to be significantly heritable (0.46±0.03 in all centers, and 0.39±0.07, 0.51±0.05, 0.44±0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD)=3.02] and in the combined sample (LOD=3.56) and on chromosome 1 (LOD=3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations.
  Human Genetics 04/2012; 126(5):667-676. · 5.07 Impact Factor
• Article: Lipoprotein-associated phospholipase A(2) mass and activity and risk of cardiovascular disease in a population with high prevalences of obesity and diabetes: the Strong Heart Study.

  Jorge R Kizer, Jason G Umans, Jianhui Zhu, Richard B Devereux, Robert L Wolfert, Elisa T Lee, Barbara V Howard
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  ABSTRACT: To investigate the association of lipoprotein-associated phospholipase A(2) (LpPLA(2)) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA(2) mass and activity were measured using commercially available assays. LpPLA(2) mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA(2) activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA(2) measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA(2) mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39-0.79]) and positive for LpPLA(2) activity (highest versus lowest tertile, 1.65 [1.12-2.42]). These associations were similar when participants with and without diabetes were examined separately. In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA(2) mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA(2) mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA(2) to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA(2) mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.
  Diabetes care 02/2012; 35(4):840-7. · 8.09 Impact Factor
• Article: Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study.

  Stacey E Jolly, Mihriye Mete, Hong Wang, Jianhui Zhu, Sven O E Ebbesson, V Saroja Voruganti, Anthony G Comuzzie, Barbara V Howard, Jason G Umans
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  ABSTRACT: It is unknown what role uric acid (UA) may play in the increasing rates of cardiovascular disease (CVD) among Alaska Eskimos. UA is associated with both hypertension (HTN) and chronic kidney disease (CKD). The authors analyzed 1078 Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) participants. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine measures using the Modification of Diet in Renal Disease equation. CKD was defined by an eGFR of <60 mL/min/1.73 m(2) . The authors adjusted for age, sex, education, diabetes, hypertension (or eGFR), obesity, lipids, and smoking status; 7% (n=75) had prevalent CKD. eGFR decreased with increasing tertiles of serum UA (P<.001). UA was independently associated with prevalent CKD (adjusted odds ratio [OR] and 95% confidence interval [CI] of 2.04 (1.62-2.56), respectively). Twenty-one percent (n=230) had prevalent HTN and UA was independently associated with prevalent HTN (adjusted OR, 1.2; 95% CI, 1.1-1.5). UA is independently associated with prevalent CKD and HTN in this population.
  Journal of Clinical Hypertension 02/2012; 14(2):71-7. · 1.83 Impact Factor
• Article: Gestational diabetes: implications for cardiovascular health.

  Shannon D Sullivan, Jason G Umans, Robert Ratner
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  ABSTRACT: Gestational diabetes mellitus (GDM) is a pregnancy complication that is becoming more prevalent with recent population trends in obesity and advancing maternal age. A diagnosis of GDM not only increases risk for maternal and fetal complications during pregnancy, but also significantly increases a woman's risk of both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in the postpartum. Even women with milder forms of abnormal glucose homeostasis during pregnancy, specifically gestational impaired glucose tolerance, are at increased risk, justifying the recent recommendation to tighten the diagnostic criteria for GDM, thus implicating many more women. Risk factors that increase risk for future CVD among women with a history of GDM include postpartum progression to T2DM; metabolic syndrome; obesity; hypertension; and altered levels of circulating inflammatory markers, specifically, adiponectin, C-reactive protein, and tumor necrosis factor-α. Medical therapies such as metformin that prevent progression to T2DM may prove to be our primary defense against earlier CVD among women with GDM.
  Current Diabetes Reports 02/2012; 12(1):43-52. · 2.50 Impact Factor
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  Available from: Jean Maccluer

  Article: Variants in CPT1A, FADS1, and FADS2 are Associated with Higher Levels of Estimated Plasma and Erythrocyte Delta-5 Desaturases in Alaskan Eskimos.

  V Saroja Voruganti, Paul B Higgins, Sven O E Ebbesson, John Kennish, Harald H H Göring, Karin Haack, Sandra Laston, Eugene Drigalenko, Charlotte R Wenger, William S Harris, [......], Jean W Maccluer, Joanne E Curran, Melanie A Carless, Matthew P Johnson, Eric K Moses, John Blangero, Jason G Umans, Barbara V Howard, Shelley A Cole, Anthony Gean Comuzzie
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  ABSTRACT: The delta-5 and delta-6 desaturases (D5D and D6D), encoded by fatty acid desaturase 1 (FADS1) and 2 (FADS2) genes, respectively, are rate-limiting enzymes in the metabolism of ω-3 and ω-6 fatty acids. The objective of this study was to identify genes influencing variation in estimated D5D and D6D activities in plasma and erythrocytes in Alaskan Eskimos (n = 761) participating in the genetics of coronary artery disease in Alaska Natives (GOCADAN) study. Desaturase activity was estimated by product: precursor ratio of polyunsaturated fatty acids. We found evidence of linkage for estimated erythrocyte D5D (eD5D) on chromosome 11q12-q13 (logarithm of odds score = 3.5). The confidence interval contains candidate genes FADS1, FADS2, 7-dehydrocholesterol reductase (DHCR7), and carnitine palmitoyl transferase 1A, liver (CPT1A). Measured genotype analysis found association between CPT1A, FADS1, and FADS2 single-nucleotide polymorphisms (SNPs) and estimated eD5D activity (p-values between 10(-28) and 10(-5)). A Bayesian quantitative trait nucleotide analysis showed that rs3019594 in CPT1A, rs174541 in FADS1, and rs174568 in FADS2 had posterior probabilities > 0.8, thereby demonstrating significant statistical support for a functional effect on eD5D activity. Highly significant associations of FADS1, FADS2, and CPT1A transcripts with their respective SNPs (p-values between 10(-75) and 10(-7)) in Mexican Americans of the San Antonio Family Heart Study corroborated our results. These findings strongly suggest a functional role for FADS1, FADS2, and CPT1A SNPs in the variation in eD5D activity.
  Frontiers in genetics. 01/2012; 3:86.
• Article: Arsenic species and selected metals in human urine: validation of HPLC/ICPMS and ICPMS procedures for a long-term population-based epidemiological study.

  Jürgen Scheer, Silvia Findenig, Walter Goessler, Kevin A Francesconi, Barbara Howard, Jason G Umans, Jonathan Pollak, Maria Tellez-Plaza, Ellen K Silbergeld, Eliseo Guallar, Ana Navas-Acien
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  ABSTRACT: Exposure to high inorganic arsenic concentrations in drinking water has been related to detrimental health effects, including cancers and possibly cardiovascular disease, in many epidemiological studies. Recent studies suggest that arsenic might elicit some of its toxic effects also at lower concentrations. The Strong Heart Study, a large epidemiological study of cardiovascular disease in American Indian communities, collected urine samples and performed medical examinations on 4,549 participants over a 10-year period beginning in 1989. We used anion-exchange HPLC/ICPMS to determine concentrations of arsenic species (methylarsonate, dimethylarsinate and arsenate) in 5,095 urine samples from the Strong Heart Study. We repeated the chromatography on a portion of the urine sample that had been oxidised, by addition of H(2)O(2), to provide additional information on the presence of As(III) species and thio-arsenicals, and by difference, of arsenobetaine and other non-retained cations. Total concentrations for As, Cd, Mo, Pb, Sb, Se, U, W, and Zn were also determined in the urine samples by ICPMS. The dataset will be used to evaluate the relationships between the concentrations of urinary arsenic species and selected metals with various cardiometabolic health endpoints. We present and discuss the analytical protocol put in place to produce this large and valuable dataset.
  Analytical methods 01/2012; 4(2):406-413. · 1.55 Impact Factor
• Article: Markers of inflammation, metabolic risk factors, and incident heart failure in American Indians: the Strong Heart Study.

  Ana Barac, Hong Wang, Nawar M Shara, Giovanni de Simone, Elizabeth A Carter, Jason G Umans, Lyle G Best, Jeunliang Yeh, Damon B Dixon, Richard B Devereux, Barbara V Howard, Julio A Panza
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  ABSTRACT: Inflammation may play a role in increased risk of heart failure (HF) that is associated with obesity, metabolic syndrome (MS), and diabetes. This study investigated associations between inflammatory markers, MS, and incident HF in a population with a high prevalence of diabetes, obesity, and MS. The cohort consisted of 3098 American Indians without prevalent cardiovascular disease who had C-reactive protein (CRP) and fibrinogen measured at the Strong Heart Study phase II examination. Independent associations between inflammatory markers, MS, and HF were analyzed by Cox hazard models. During a mean follow-up of 11 years, 218 participants developed HF. After the adjustment for cardiovascular risk factors, fibrinogen, (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.15-1.59) but not CRP (HR, 1.25; 95% CI, 0.97-1.32) remained a significant HF predictor. In individuals without diabetes, concomitant presence of MS and elevated CRP or fibrinogen increased HF risk (for MS and CRP: HR, 2.02; 95% CI, 0.95-4.31; for CRP and fibrinogen: HR, 1.75; 95% CI, 0.83-3.72). In a population with a high prevalence of obesity, MS, and diabetes, elevated CRP and fibrinogen increased HF risk. These associations are attenuated by the adjustments for conventional risk factors suggesting that inflammation acts in concert with metabolic and clinical risk factors in increasing HF risk.
  Journal of Clinical Hypertension 01/2012; 14(1):13-9. · 1.83 Impact Factor
• Article: Incremental value of biochemical and echocardiographic measures in prediction of ischemic stroke: the Strong Heart Study.

  Maria G Karas, Richard B Devereux, David O Wiebers, Jack P Whisnant, Lyle G Best, Elisa T Lee, Barbara V Howard, Mary J Roman, Jason G Umans, Jorge R Kizer
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  ABSTRACT: American Indians have high rates of stroke. Improved risk stratification could enhance prevention, but the ability of biochemical and echocardiographic markers of preclinical disease to improve stroke prediction is not well-defined. We evaluated such markers as predictors of ischemic stroke in a community-based cohort of American Indians without prevalent cardiovascular or renal disease. Laboratory markers included C-reactive protein, fibrinogen, urine albumin-to-creatinine ratio, and glycohemoglobin (HbA1c), whereas echocardiographic parameters comprised left atrial diameter, left ventricular mass, mitral annular calcification, and the ratio of early to late mitral diastolic velocities. Predictive performance was judged by indices of discrimination, reclassification, and calibration. After adjustment for standard risk factors, only HbA1c, albuminuria, and left atrial diameter were significantly associated with first ischemic stroke. Addition of HbA1c, although not urine albumin-to-creatinine ratio, to a basic clinical model significantly improved the C-statistic (0.714 versus 0.695; P=0.044), whereas left atrial diameter modestly enhanced integrated discrimination improvement (0.90%; P=0.004), but not the C-statistic (0.701; P=0.528). When combined with HbA1c, left atrial diameter further increased integrated discrimination improvement (1.81%; P<0.001) but not the C-statistic (0.716). No marker achieved significant net reclassification improvement. In this cohort at high cardiometabolic risk, HbA1c emerged as the foremost predictor of ischemic stroke when added to traditional risk factors, affording substantially improved discrimination, with a more modest contribution for left atrial diameter. These findings bolster the role of HbA1c in cardiovascular risk assessment among persons with glycometabolic disorders and provide impetus for further study of the incremental value of echocardiography in high-risk populations.
  Stroke 12/2011; 43(3):720-6. · 5.73 Impact Factor