Lisa Martin

Publications (109) View all

• Article: Insulin resistance and arterial stiffness in healthy adolescents and young adults.

  E M Urbina, Z Gao, P R Khoury, L J Martin, L M Dolan
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  ABSTRACT: Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors. We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness. Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx R²= 0.34; BrachD R² = 0.37; PWV R² = 0.40; all p ≤ 0.02). Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.
  Diabetologia 12/2011; 55(3):625-31. · 6.81 Impact Factor
• Article: Gender differences in the relationships among obesity, adiponectin and brachial artery distensibility in adolescents and young adults.

  E M Urbina, P Khoury, L J Martin, D D'Alessio, L M Dolan
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  ABSTRACT: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. We compared brachial artery distensibility (BrachD) with APN, the level of adiposity and other CV risk factors (CVRFs) in 431 post-pubertal subjects (mean 17.9 years). Gender differences in average values were examined by t-tests. Correlations among BrachD, obesity and other CVRFs were examined. Regression analysis was performed to determine whether APN provided an independent contribution to BrachD, while controlling for obesity and other CVRFs. Male subjects had lower BrachD (5.72+/-1.37 vs 6.45+/-1.60% change per mm Hg, P<0.0001) and lower APN (10.50+/-4.65 vs 13.20+/-6.53; all P<0.04) than female subjects. BrachD correlated with APN (r=0.25, P< 0.0001). Both BrachD and APN correlated with measures of body size, including height, weight and body mass index (BMI). Both correlated with higher systolic blood pressure, glucose, insulin and lower high-density lipoprotein cholesterol (all P<0.01). In multivariate analysis, APN, gender, APN*gender and BMI z-score predicted BrachD (r(2)=0.305). On the basis of gender difference, only BMI z-score was significant for male subjects (r(2)=0.080), whereas APN and BMI z-score contributed for female subjects (r(2)=0.242, all P<0.0001). BrachD is independently influenced by obesity in both male and female subjects. In female subjects, APN exerts an additional independent effect even after adjusting for blood pressure (BP), lipid levels and insulin. Differences in the effect of the APN-adiposity relationship on obesity-related vascular disease may be one reason for gender differences in the development and progression of atherosclerosis.
  International journal of obesity (2005) 08/2009; 33(10):1118-25. · 4.34 Impact Factor
• Article: High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders.

  J Pablo Abonia, Ting Wen, Emily M Stucke, Tommie Grotjan, Molly S Griffith, Katherine A Kemme, Margaret H Collins, Philip E Putnam, James P Franciosi, Karl F von Tiehl, Brad T Tinkle, Keith A Marsolo, Lisa J Martin, Stephanie M Ware, Marc E Rothenberg
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  ABSTRACT: BACKGROUND: Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. OBJECTIVE: We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). METHODS: We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. RESULTS: We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ(2)1 = 112.0; P < 10(-3)) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. CONCLUSION: There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD.
  The Journal of allergy and clinical immunology 04/2013; · 9.17 Impact Factor
• Article: Fractures in children with neurofibromatosis type 1 from two NF clinics.

  Jaya K George-Abraham, Lisa J Martin, Heidi J Kalkwarf, Margaret B Rieley, David A Stevenson, David H Viskochil, Robert J Hopkin, Austin M Stevens, Heather Hanson, Elizabeth K Schorry
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  ABSTRACT: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with osseous abnormalities occurring in up to one-third of patients. Several studies have documented osteopenia in both children and adults with NF1; however, the significance of lower bone mineral density (BMD) in relationship to fracture incidence is not well elucidated in NF1, particularly in children. We undertook a retrospective study to determine prevalence and location of fractures in children and adolescents with NF1, ages 5-20 years, using a standardized questionnaire. We surveyed 256 individuals with NF1 from two multidisciplinary NF centers and 178 controls without NF1 of similar ages and sex. Participants with known long bone dysplasia (LBD) were analyzed separately. Data collected included numbers and location of fractures, dietary calcium intake, and physical activity levels. There was no difference in prevalence of ever having a fracture between the NF1 group without LBD (22%) and the control group (25%); median number of fractures also did not differ. There were significant differences in fracture location with a higher frequency of fractures of the lower extremities in NF1 individuals without LBD compared to controls. Both NF1 cohorts had lower rates of physical activity than controls (P < 0.0001). Our data demonstrate that the likelihood of having had a fracture is not higher in young NF1 individuals without LBD in comparison to healthy controls. The lower physical activity level may have a "protective effect" for those with NF1, thus keeping their fracture incidence lower than expected for their relative degree of osteopenia. © 2013 Wiley Periodicals, Inc.
  American Journal of Medical Genetics Part A 03/2013; · 2.39 Impact Factor
• Source

  Available from: Jessica G Woo

  Article: Quantitative criteria for improving performance of buccal DNA for high-throughput genetic analysis.

  Jessica G Woo, Lisa J Martin, Lili Ding, W Mark Brown, Timothy D Howard, Carl D Langefeld, Charles J Moomaw, Mary Haverbusch, Guangyun Sun, Subba R Indugula, Hong Cheng, Ranjan Deka, Daniel Woo
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  ABSTRACT: DNA from buccal brush samples is being used for high-throughput analyses in a variety of applications, but the impact of sample type on genotyping success and downstream statistical analysis remains unclear. The objective of the current study was to determine laboratory predictors of genotyping failure among buccal DNA samples, and to evaluate the successfully genotyped results with respect to analytic quality control metrics. Sample and genotyping characteristics were compared between buccal and blood samples collected in the population-based Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study (https://gerfhs.phs.wfubmc.edu/public/index.cfm). Seven-hundred eight (708) buccal and 142 blood DNA samples were analyzed for laboratory-based and analysis metrics. Overall genotyping failure rates were not statistically different between buccal (11.3%) and blood (7.0%, p = 0.18) samples; however, both the Contrast Quality Control (cQC) rate and the dynamic model (DM) call rates were lower among buccal DNA samples (p < 0.0001). The ratio of double-stranded to total DNA (ds/total ratio) in the buccal samples was the only laboratory characteristic predicting sample success (p < 0.0001). A threshold of at least 34% ds/total DNA provided specificity of 98.7% with a 90.5% negative predictive value for eliminating probable failures. After genotyping, median sample call rates (99.1% vs. 99.4%, p < 0.0001) and heterozygosity rates (25.6% vs. 25.7%, p = 0.006) were lower for buccal versus blood DNA samples, respectively, but absolute differences were small. Minor allele frequency differences from HapMap were smaller for buccal than blood samples, and both sample types demonstrated tight genotyping clusters, even for rare alleles. We identified a buccal sample characteristic, a ratio of ds/total DNA <34%, which distinguished buccal DNA samples likely to fail high-throughput genotyping. Applying this threshold, the quality of final genotyping resulting from buccal samples is somewhat lower, but compares favorably to blood. Caution is warranted if cases and controls have different sample types, but buccal samples provide comparable results to blood samples in large-scale genotyping analyses.
  BMC Genetics 08/2012; 13(1):75. · 2.47 Impact Factor