Carlos A Aguilar-Salinas

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpam, Mexico City, Mexico

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Publications (215)741.49 Total impact

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    ABSTRACT: A higher prevalence of metabolic syndrome (MetS) has been described in rheumatoid arthritis (RA), along with an association with disease activity. Objectives were to describe prevalence of MetS at RA diagnosis in a cohort of Mexican Mestizo early RA patients, and to define a causal association between MetS and disease activity. The study population was a prospective cohort. At baseline and at fixed 6-months-intervals, patients had medical evaluations, fasting serum glucose, triglycerides, high-density lipoprotein cholesterol and acute reactant-phase determinations. MetS was defined according to international criteria and body mass index (BMI) ≥30 kg/m(2) was used as a surrogate of the waist circumference. The study was approved by the internal review board. Appropriated statistics and Cox regression analysis were used. All statistical tests were two-sided and evaluated at the 0.05 significance level. Up to March 2014, data from 160 patients were analyzed. At baseline, they were more frequently middle-aged females and had moderate to high disease activity. Prevalence of MetS varied from 11.3% to 17.5% in patients and was lower to that from matched controls (versus 26.3% to 30%, P ≤0.01). Up to last follow-up, 39 patients (34.5%) developed incidental MetS. In the Cox regression analysis, cumulative disease activity score (DAS) 28 (odds ratio (OR): 1.81, 95% confidence interval (CI): 1.346 to 2.433, P = 0.000) and baseline BMI (OR: 1.13, 96% CI: 1.035 to 1.236, P = 0.007) were the only predictors for incidental MetS. RA patients with incidental MetS accumulated more disease activity and had less frequent remission than their counterparts. Logistic regression analysis showed that incidental MetS (OR: 0.2, 95% CI: 0.01 to 0.99, P = 0.052) and baseline DAS28 (OR: 0.4, 95% CI: 0.2 to 0.9, P = 0.02) were the only predictors for achieving or maintaining sustained (≥6 months) remission. MetS prevalence in a cohort of early RA patients was lower than that from matched controls. Cumulative disease activity and higher BMI were risk factors for incidental Mets; higher baseline disease activity and incidental MetS prevented sustained remission. In addition to disease activity, MetS needs to be controlled to impact disease outcomes.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0549-x · 4.12 Impact Factor
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    ABSTRACT: Treatment of cardiovascular risk factors based on disease risk depends on valid risk prediction equations. We aimed to develop, and apply in example countries, a risk prediction equation for cardiovascular disease (consisting here of coronary heart disease and stroke) that can be recalibrated and updated for application in different countries with routinely available information. We used data from eight prospective cohort studies to estimate coefficients of the risk equation with proportional hazard regressions. The risk prediction equation included smoking, blood pressure, diabetes, and total cholesterol, and allowed the effects of sex and age on cardiovascular disease to vary between cohorts or countries. We developed risk equations for fatal cardiovascular disease and for fatal plus non-fatal cardiovascular disease. We validated the risk equations internally and also using data from three cohorts that were not used to create the equations. We then used the risk prediction equation and data from recent (2006 or later) national health surveys to estimate the proportion of the population at different levels of cardiovascular disease risk in 11 countries from different world regions (China, Czech Republic, Denmark, England, Iran, Japan, Malawi, Mexico, South Korea, Spain, and USA). The risk score discriminated well in internal and external validations, with C statistics generally 70% or more. At any age and risk factor level, the estimated 10 year fatal cardiovascular disease risk varied substantially between countries. The prevalence of people at high risk of fatal cardiovascular disease was lowest in South Korea, Spain, and Denmark, where only 5-10% of men and women had more than a 10% risk, and 62-77% of men and 79-82% of women had less than a 3% risk. Conversely, the proportion of people at high risk of fatal cardiovascular disease was largest in China and Mexico. In China, 33% of men and 28% of women had a 10-year risk of fatal cardiovascular disease of 10% or more, whereas in Mexico, the prevalence of this high risk was 16% for men and 11% for women. The prevalence of less than a 3% risk was 37% for men and 42% for women in China, and 55% for men and 69% for women in Mexico. We developed a cardiovascular disease risk equation that can be recalibrated for application in different countries with routinely available information. The estimated percentage of people at high risk of fatal cardiovascular disease was higher in low-income and middle-income countries than in high-income countries. US National Institutes of Health, UK Medical Research Council, Wellcome Trust. Copyright © 2015 Elsevier Ltd. All rights reserved.
    03/2015; DOI:10.1016/S2213-8587(15)00081-9
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    ABSTRACT: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near/in PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes associated with non-alcoholic fatty liver disease (NAFLD) mainly in individuals of European ancestry. The aim of the study was to test whether these genetic variants and a genetic risk score (GRS) are associated with elevated liver fat content and non-alcoholic steatohepatitis (NASH) in Mexicans with morbid obesity. 130 morbidly obese Mexican individuals were genotyped for six SNPs in/near PNPLA3, NCAN, LYPLAL1, PPP1R3B, and GCKR genes. Hepatic fat content [triglyceride (HTG) and total cholesterol (HTC)] was quantified directly in liver biopsies and NASH was diagnosed by histology. A GRS was tested for association with liver fat content and NASH using logistic regression models. In addition, 95 ancestry-informative markers were genotyped to estimate population admixture proportions. After adjusting for age, sex and admixture, PNPLA3, LYPLAL1, GCKR and PPP1R3B polymorphisms were associated with higher HTG content (P<0.05 for PNPLA3, LYPLAL1, GCKR polymorphisms and P=0.086 for PPP1R3B). The GRS was significantly associated with higher HTG and HTC content (P=1.0×10(-4) and 0.048, respectively), steatosis stage (P=0.029), and higher ALT levels (P=0.002). Subjects with GRS ≥6 showed a significantly increased risk of NASH (OR=2.55, P=0.045) compared to those with GRS ≤5. However, the GRS did not predict NASH status, as AUC of ROC curves was 0.56 (P=0.219). NAFLD associated loci in Europeans and a GRS based on these loci contribute to the accumulation of hepatic lipids and NASH in morbidly obese Mexican individuals. Copyright © 2015. Published by Elsevier Inc.
    Experimental and Molecular Pathology 01/2015; DOI:10.1016/j.yexmp.2015.01.012 · 2.88 Impact Factor
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    ABSTRACT: Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components although few studies have examined their genetic architecture or their influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multi-cohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently-sampled intravenous glucose tolerance test (4 cohorts) or euglycemic clamp (3 cohorts) and random effects models were used to test association between loci and quantitative traits, adjusting for age, gender, and admixture proportions (Discovery). Analysis revealed significant (P<5.00x10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P<0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D cases and 9,232 controls of Mexican ancestry (Translation). Non-parametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive risk for T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes 12/2014; DOI:10.2337/db14-0732 · 8.47 Impact Factor
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    ABSTRACT: Alterations in postprandial metabolism have been described in familial combined hyperlipidemia (FCH); however, their underlying mechanisms are not well characterized. We aimed to identify factors related to the magnitude of postprandial lipemia and apolipoprotein (apo) A-V levels in subjects with FCH. FCH cases (n = 99) were studied using a standardized meal test. Abdominal obesity was assessed using the waist to hip ratio (WHR). A linear regression model was performed to investigate the variables associated with the triglycerides incremental area under the curve (iAUC). Independent associations between metabolic variables and apo A-V iAUC were also investigated in a randomly selected subgroup (n = 44). The study sample was classified according to the presence of fasting hypertriglyceridemia (>=150 mg/dL) and abdominal obesity (WHR >=0.92 in men and >=0.85 in women) to explore differences in parameters. The fasting apo B-48 levels (r = 0.404), and the WHR (r = 0.359) were independent factors contributing to the triglycerides iAUC (r2 = 0.29, P < 0.001). The triglycerides iAUC was independently associated with the apo A-V iAUC (r2 = 0.54, P < 0.01). Patients with both hypertriglyceridemia and abdominal obesity showed the most robust triglycerides and apo A-V postprandial responses. In patients with FCH the fasting apo B-48 level is the main factor associated with postprandial lipemia. Abdominal obesity also contributes to the magnitude of the postprandial response.The triglycerides postprandial increment is the principal factor associated with the apo A-V postprandial response.
    BMC Endocrine Disorders 11/2014; 14(1):90. DOI:10.1186/1472-6823-14-90 · 1.67 Impact Factor
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    ABSTRACT: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE. Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD). The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD. We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
    Medicina Clínica 11/2014; 144(7). DOI:10.1016/j.medcli.2014.06.018 · 1.25 Impact Factor
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    ABSTRACT: Empowerment interventions for chronic diseases are an evolving process. No agreement exists regarding the necessary components and methodologies to be applied. Systematic reviews have assessed the effect of self-management interventions. Improvements in illness beliefs, adherence to drug therapy and glucose monitoring have been reported. In the long term, no major changes have been achieved in weight, physical activity, smoking status, and depression scores. There is a need for additional studies. The CAIPaDi (Centro de Atención Integral del Paciente con Diabetes) program is an intervention designed to provide education and empowerment techniques (using simple low-cost interactive tools) over a short period of time followed by at-distance support using internet or cell phone technology. The target population consists of patients with type 2 diabetes, free of chronic complications who are non-smokers. The intervention is composed of four monthly visits followed by a continuous at-distance support system. At each visit, patients stay for six hours in the center. Information is presented in group sessions. Empowerment techniques are applied during individual exchanges with the team or during facilitated group sessions. In summary, empowerment programs are an unmet need in many healthcare services. This review also discusses relevant studies and patents in the management of type 2 diabetes.
    Recent Patents on Endocrine Metabolic & Immune Drug Discovery 11/2014; 8(3). DOI:10.2174/1872214808999141110155515
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    ABSTRACT: Background: In familial combined hyperlipidemia (FCHL) the severity of the dyslipidemia is determined by an overproduction of VLDL (very low density lipoprotein) particles and by its abnormal lipid composition. However, few are known regarding the metabolic factors that determine these abnormalities. We investigated the impact of metabolic factors on the number of atherogenic particles (apolipoprotein B level (apoB)) and the triglyceride content of very low-density lipoproteins (VLDLs-TG). Methods: A cross-sectional study done in FCHL subjects and gender and age-matched healthy subjects. A clinical assessment, lipid profile and plasma concentrations of insulin, apolipoprotein CIII (apo CIII), apolipoprotein All (apo All), high sensitive C-reactive protein (HS-CRP), adiponectin and leptin were documented in 147 FCHL patients and 147 age-matched healthy subjects. Multivariate regression models were performed to investigate the independent determinants of VLDL-TG and apo B levels adjusting for confounding factors. Results: The variables that determined the VLDL-triglyceride content as a surrogate of VLDL composition were apo CIII (beta = 0365, p < 0.001), insulin (beta = 0281, p < 0.001), Apo All (beta = 0.145, p < 0.035), and adiponectin levels (beta = -0255, p < 0.001). This model explained 34% of VLDL composition (VLDL-TG) variability. However, none of these variables were independent contributors of apo B-containing particles. Conclusions: In patients with FCHL apo CIII, apo All and adiponectin are major novel factors determining the VLDL particle composition. However, such factors do not explain apo B-containing particles.
    Clinica Chimica Acta 08/2014; 438. DOI:10.1016/j.cca.2014.08.018 · 2.76 Impact Factor
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  • Carlos A. Aguilar-Salinas, Teresa Tusie-Luna, Päivi Pajukanta
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    ABSTRACT: Here, we discuss potential explanations for the higher prevalence of hypertriglyceridemia in populations with an Amerindian background. Although environmental factors are the triggers, the search for the ethnic related factors that explains the increased susceptibility of the Amerindians is a promising area for research. The study of the genetics of hypertriglyceridemia in Hispanic populations faces several challenges. Ethnicity could be a major confounding variable to prove genetic associations. Despite that, the study of hypertriglyceridemia in Hispanics has resulted in significant contributions. Two GWAS reports have exclusively included Mexican mestizos. Fifty percent of the associations reported in Caucasians could be generalized to the Mexicans, but in many cases the Mexican lead SNP was different than that reported in Europeans. Both reports included new associations with apo B or triglycerides concentrations. The frequency of susceptibility alleles in Mexicans is higher than that found in Europeans for several of the genes with the greatest effect on triglycerides levels. An example is the SNP rs964184 in APOA5. The same trend was observed for ANGPTL3 and TIMD4 variants. In summary, we postulate that the study of the genetic determinants of hypertriglyceridemia in Amerindian populations which have major changes in their lifestyle, may prove to be a great resource to identify new genes and pathways associated with hypertriglyceridemia.
    Metabolism: clinical and experimental 07/2014; DOI:10.1016/j.metabol.2014.03.012 · 3.61 Impact Factor
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    ABSTRACT: Artículo original Utilidad de la proteína C reactiva y velocidad de sedimentación globular para la detección de osteomielitis en pie diabético Resumen Introducción: Dentro de las situaciones de mayor gravedad en el pie diabé-tico se encuentra la presencia de osteomielitis. Se han buscado marcadores diagnósticos indirectos, no invasivos, confiables y de amplia disponibilidad, entre los que se han postulado la velocidad de sedimentación globular (VSG) y la proteína C reactiva (PCR). Objetivos: Comparar los niveles séricos de la PCR y de la VSG como indicadores de osteomielitis en pacientes aten-didos por pie diabético. Material y métodos: Se revisaron los expedientes clínicos del Hospital General Manuel Gea González con el diagnóstico de pie diabético en el periodo comprendido de enero de 2005 a diciembre de 2009. Se registraron variables clínicas, de laboratorio y gabinete, siendo analizadas con los desenlaces de amputación y osteomielitis. Resultados: Se incluyeron en el análisis 80 pacientes. El tiempo de evolución del diag-nóstico de diabetes es de 7.6 años. Las principales comorbilidades fueron tabaquismo (51% de los pacientes), amputación previa (40%) e hipertensión (32.5%). Se reportaron cambios radiológicos compatibles con osteomielitis en 18 pacientes (22.5%). Cuarenta y seis enfermos (57.5%) fueron sometidos a cirugía de amputación. El estudio histopatológico reportó osteomielitis en el 19.5%, infección de tejidos blandos en un 8.7% y ateroesclerosis en 58.7%. Con relación al desenlace quirúrgico se encontró significancia estadística de amputación con concentración más elevada de PCR (10.7 ± 8 vs 5.6 ± 5.8, p = 0.004), marginalmente con VSG (83.1 ± 5 vs 64.8 ± 39, p = 0.04), mayor tiempo de evolución de la diabetes (11.1 ± 9 vs 2.4 ± 2.5, p = 0.001) y la presencia de leucocitosis (13.8 ± 6 vs 8.4 ± 4, p = 0.001). En el análisis de curva ROC para osteomielitis, el área para PCR fue de 0.551 (IC 95%, 0.36-0.75) y para VSG fue 0.712 (IC 95%, 0.55-0.87). Conclusión: Los pacientes con pie diabético presentan varios factores de riesgo cardiovascular y complicaciones micro y macrovasculares. Los facto-res de riesgo asociados a amputaciones fueron mayor tiempo de evolución de la diabetes, PCR elevada y leucocitosis. La velocidad de sedimentación globular tiene mayor valor diagnóstico para osteomielitis en comparación con la proteína C reactiva. Palabras clave: Pie diabético, osteomielitis, amputación, velocidad de sedimentación globular, proteína C reactiva. Abstract Introduction: One of the major problems in diabetic foot is osteomyelitis. Many non-invasive, indirect, reliable and widely available biomarkers have been tested, being some of these the erythrocyte sedimentation rate (ESR) and the C reactive protein (CRP). Objectives: Compare serum levels of CRP and ESR as indicators of osteomyelitis in patients with diabetic foot. Material and methods: Clinical files in the Hospital General Dr. Manuel Gea González with the diagnosis of diabetic foot were analyzed in the pe-riod between January 2005 and December 2009. Clinical, laboratory and radiological variables were registered, being analyzed with the outcomes of amputation and osteomyelitis. Results: Eighty patients were included in the analysis. The time of the diagnosis of diabetes was 7.6 years. The main comorbidities were smoking (51% of patients), previous amputation (40%) and hypertension (32.5%). Radiological changes compatible with osteomyelitis were seen in 18 patients (22.5%). Forty six patients (57.5%) had surgical amputation. Twenty eight patients without radiological signs of osteomyelitis had amputation. The hystopathological study reported osteomyelitis in 19.5%, soft tissue infection in 8.7% and atherosclerosis in 58.7%. In relation to the surgical outcome, there was statistical signifi-cance for amputation with high concentrations of CRP (10.7 ± 8 vs 5.6 ± 5.8, p = 0.004), marginally with ESR (83.1 ± 5 vs 64.8 ± 39, p = 0.04), more time of diabetes (11.1 ± 9 vs 2.4 ± 2.5, p = 0.00) and presence of leucocytosis (13.8 ± 6 vs 8.4 ± 4, p = 0.00). In the ROC analysis for osteomyelitis, the area for CRP was 0.551 (IC 95%, 0.36-0.75) and for ESR was 0.712 (IC 95%, 0.55-0.87). Conclusion: Patients with diabetic foot present many cardiovascular risk factors and micro and macrovascular complications associated with diabetes. The risk factors associated with amputation were longer history of diabetes, high levels of CRP and leuco-cytosis. The ESR has a greater diagnostic value for osteomyelitis than CRP.
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    ABSTRACT: The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels. The study included a total of 1624 Mexican individuals: 919 Indigenous subjects from five different native groups and 705 Mexican Mestizo individuals (141 cases with ALT levels ≥40 U/L and 564 controls with ALT <40 U/L). The I148M polymorphism was genotyped by TaqMan assays. The frequency of elevated ALT levels in Indigenous populations was 18.7 %, and varied according to obesity status: 14.4 % in normal weight, 19.9 % in overweight and 24.5 % in obese individuals. The Mexican indigenous populations showed the highest reported frequency of the PNPLA3 148M risk allele (mean 0.73). The M148M genotype was significantly associated with elevated ALT levels in indigenous individuals (OR = 3.15, 95 % CI 1.91-5.20; P = 7.1 × 10(-6)) and this association was confirmed in Mexican Mestizos (OR = 2.24, 95 % CI 1.50-3.33; P = 8.1 × 10(-5)). This is the first study reporting the association between M148M genotype and elevated ALT levels in Indigenous Mexican populations. The 148M allele risk may be considered an important risk factor for liver damage in Mexican indigenous and Mestizo populations.
    Molecular Biology Reports 04/2014; DOI:10.1007/s11033-014-3341-0 · 1.96 Impact Factor
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    ABSTRACT: Latin America is among the regions with the highest diabetes-related burden. Research and treatment programs have increased in number and complexity in recent years, but they are focused in type 2 diabetes, because this condition explains a large proportion of the cases. In contrast, the information regarding the epidemiology of type 1 diabetes is scant in this area. Here, we analyze the available information on this topic and identify potential areas of opportunity to generate new knowledge through the study of type 1 diabetes in Latin Americans. Both, the prevalence and the incidence of type 1 diabetes, are lower in Latin American countries compared to that reported in Europe, North America, southern Asia and northern Africa. Biologic and methodological factors may explain the smaller contribution of type 1. The presence of some putative 'protective' environmental exposures or the absence of those prevalent in a region may explain the lower type 1 diabetes prevalence observed in most Latin American countries. However, the number and quality of the diabetes registries are not enough in this region. During the past decade, the incidence of type 1 diabetes has grown worldwide. The same trend has been reported in Latin America. This epidemiologic transition is a unique opportunity to identify interactions between rapidly changing environmental factors in subjects with different genetic backgrounds (such as the admixed Latin American populations). Finally, on-going therapeutic initiatives in this region are highlighted.
    Current diabetes reviews 02/2014; DOI:10.2174/1573399810666140223183936
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    ABSTRACT: Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican-Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans.
    Nature Communications 01/2014; 5:3983. DOI:10.1038/ncomms4983 · 10.74 Impact Factor
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    ABSTRACT: Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10−13; odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10−4; OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.
    Nature 12/2013; DOI:10.1038/nature12828 · 42.35 Impact Factor
  • Raúl Julián Ortiz-Bautista, Carlos Alberto Aguilar-Salinas, Adriana Monroy-Guzmán
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    ABSTRACT: Caloric restriction, as a 30 to 60% decrease of ad libitum balanced caloric intake, without malnutririon, is the non-genetic strategy that has consistently extended the average and maximum lifespan of most living beings, and it has been tested from unicellular organisms like yeast Saccharomyces cerevisiae to Rhesus primates. In addition, various genetic and pharmacological caloric restriction models have shown to protect against cancer, cardiovascular and neurodegenerative diseases. Primate studies suggest that this intervention delays the onset of age-related diseases; in humans, it has physiological, biochemical and metabolic effects decreasing diabetes and cardiovascular disease risk factor. Although currently the mechanism by which caloric restriction has its positive effects at the cellular level is unknown, it has been reported to decrease oxidative stress and increase in mitochondrial biogenesis.
    Cirugia y cirujanos 09/2013; 81(5):459-64. · 0.32 Impact Factor
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    ABSTRACT: Several studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos. 9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults. After adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations. Our findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children.
    PLoS ONE 08/2013; 8(8):e70640. DOI:10.1371/journal.pone.0070640 · 3.53 Impact Factor

Publication Stats

3k Citations
741.49 Total Impact Points

Institutions

  • 2001–2015
    • Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
      • Department of Immunology and Rheumatology
      Tlalpam, Mexico City, Mexico
    • Autonomous University of Nuevo León
      San Nicolás de los Garza, Nuevo León, Mexico
  • 2011
    • Special Regional Hospital of Oaxaca
      Santa Maria, Oaxaca, Mexico
    • The University of the West Indies at Mona
      • Department of Basic Medical Sciences
      Kingston, Kingston, Jamaica
    • Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF)
      Ciudad de México, Mexico City, Mexico
  • 2008–2011
    • University of California, Los Angeles
      • Department of Human Genetics
      Los Angeles, CA, United States
  • 2009
    • Universidad Autónoma de Veracruz
      Xalapa, Veracruz-Llave, Mexico
  • 2005–2007
    • Universidad Nacional Autónoma de México
      Ciudad de México, The Federal District, Mexico
  • 2004–2007
    • Mexican Institute of Social Security
      Ciudad de México, The Federal District, Mexico
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2006
    • University of Helsinki
      Helsinki, Uusimaa, Finland
    • Mountain View College
      Mountain View, California, United States