Nancy Martínez-Rodríguez

Single Nucleotide Polymorphisms of the Angiotensin-Converting Enzyme (ACE) Gene Are Associated with Essential Hypertension and Increased ACE Enzyme Levels in Mexican Individuals

Aim To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. Methods Nine ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. Results Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048). Conclusion The results suggest that single nucleotide polymorphisms and the “GGATG” haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.

β 1 Adrenergic Receptor Polymorphisms Arg389Gly and Ser49Gly in the Amerindian and Mestizo Populations of Mexico

The β1 adrenergic receptor genotypes (Ser49Gly and Arg389Gly) were determined in 190 individuals from 3 Mexican populations. Mestizos and Teenek present the highest frequencies for the *Arg allele and the lowest frequencies for the *Gly allele (Arg389Gly) compared to European, Asian, and African populations. Mayos present the highest frequency for the *Gly allele. The knowledge of the distribution of these alleles could help define the significance of these polymorphisms as genetic susceptibility markers in Amerindian populations.

The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study.

The aim of the present study was to establish the role of HIF1A gene polymorphisms in the risk of developing premature coronary artery disease (CAD) in a well-characterized clinical cohort. Three polymorphisms in HIF1A (rs11549465, rs11549467, rs2057482) gene were genotyped in 949 patients with premature CAD, and 676 healthy controls (with negative calcium score by computed tomography). Under a dominant model adjusted for age, visceral to subcutaneous adipose tissue (VAT/SAT) ratio, hypertension, type 2 diabetes mellitus (T2DM), HDL-C levels, hypercholesterolemia and hypertriglyceridemia, the rs2057482 T allele was associated with decreased risk of premature CAD when compared to healthy controls (OR = 0.616, P(dom) = 0.020). The effect of the studied polymorphisms on various metabolic parameters and cardiovascular risk factors was explored. In this analysis, the rs2057482 T allele was associated with decreased risk of obesity, central obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and increased risk of T2DM. Under a dominant model adjusted by age, the HIF1A rs2057482 T polymorphism was associated with high VAT/SAT ratio (P = 0.009) and HDL-C levels (P = 0.04) in healthy controls. The results suggest that HIF1A rs2057482 polymorphism is involved in the risk of developing CAD and is associated with some metabolic parameters and cardiovascular risk factors.

Association of angiotensin II type 1-receptor gene polymorphisms with the risk of developing hypertension in Mexican individuals.

Introduction: Hypertension is a complex disease in which a significant interaction between genetic and environmental factors takes place. The renin–angiotensin system plays an important role regulating blood pressure to maintain homeostasis and vascular tone. In the present work, the role of angiotensin II type 1-receptor (AGTR1) gene polymorphisms as susceptibility markers for hypertension was evaluated. Materials and methods: Five polymorphisms in the AGTR1 gene were genotyped by 5′ exonuclease TaqMan genotyping assays in 239 hypertensive and 371 non-hypertensive individuals. Results: A similar distribution of rs275651, rs275652, rs275653, and rs5183 polymorphisms was observed in both studied groups. Different distribution of rs5182 genotypes was observed between the studied groups (p = 0.016). According to the co-dominant model, individuals with rs5182 CC genotype have a 1.83-fold increased risk of developing hypertension (p = 0.009). Polymorphisms were distributed in two blocks: block 1 included the rs275651, rs275652, and rs275653 polymorphisms, whereas block 2 included the rs5183 and rs5182 polymorphisms. Individuals with hypertension showed increased frequency of ‘CA’ haplotype of block 2 when compared to non-hypertensive individuals (p = 0.015, odds ratio = 1.33). Conclusion: The results suggest that the rs5182 gene polymorphism could be involved in the risk of developing hypertension in Mexican individuals.

Matrix γ-Carboxyglutamic Acid Protein (MGP) G-7A and T-138C Gene Polymorphisms in Indian (Mayo and Teenek) and Mestizo Populations from Mexico

Matrix γ-carboxyglutamic acid protein (MGP) genotypes (G-7A and T-138C) were determined in 266 individuals from three Mexican populations. Mexicans showed increased frequencies of the G-7A G allele and the G7-A GG genotype compared to Europeans. For the T-138C genotype, we found differences among the Mexicans. This study could help to define the significance of MGP polymorphisms as genetic markers in Amerindian populations.

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population.

Single-nucleotide polymorphisms (SNPs) in the protein phosphatase and actin regulator 1 gene (PHACTR1) have been associated with susceptibility to develop several diseases, including cardiovascular disease. The purpose of this study was to evaluate the role of two polymorphisms (rs2026458 and rs9349379) of the PHACTR1 gene in the susceptibility to the risk of developing premature coronary artery disease (CAD) in the Mexican population. The genotype analysis was performed using 5’exonuclease TaqMan genotyping assays in a group of 994 patients with premature CAD and 703 controls. A similar genotype distribution of rs2026458 was observed in both groups; however, under an additive model adjusted by age, body mass index, type 2 diabetes mellitus, smoking, dyslipidemia, and hypertension, the rs9349379 G allele was associated with a higher risk for developing premature CAD (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.03–1.46, p-value (p) = 0.024). The two PHACTR1 polymorphisms were not in linkage disequilibrium. In summary, our results suggest that the PHACTR1 rs9349379 polymorphism plays an important role in the risk of developing premature CAD in the Mexican population.

TIMP2 gene polymorphisms are associated with hypertension in patients with myocardial infarction

Previous studies have revealed that tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in atherosclerosis and plaque disruption (Cheng et al. 2008). The present study analysed the role of TIMPs gene polymorphisms in the risk of developing myocardial infarction (MI) in a cohort of Mexican Mestizo patients. MI patients were classified into clinical subgroups according to cardiovascular risk factors. Multiple logistic regression models were performed to analyse genetic data. Under different models of heritage, adjusted by age, gender, type 2 diabetes mellitus, and smoking habits, the TIMP2 rs4789932 C allele was associated with decreased risk of hypertension (P = <0.05), TIMP2 rs7501477 T allele was associated with increased risk of hypertension (P = <0.05). The data suggest that TIMP2 gene polymorphisms are associated with hypertension in Mexican patients with myocardial infarction. Coronary artery disease (CAD) and one of its manifestations, MI, is a major cause of death worldwide. Increased expression of several metalloproteinases (MMPs) has been observed in diseased human arteries and in association with arterial morphological changes in experimental models of atherosclerosis (Newby 2005). Studies have shown an

Protective role of DDAH2 (rs805304) gene polymorphism in patients with myocardial infarction.

The purpose of the present study was to establish the role of DDAH gene polymorphisms in the risk of developing myocardial infarction (MI) in a clinical cohort of Mexican patients. One polymorphism (rs1498373) in the DDAH1 and three in the DDAH2 (rs805304, rs3131383, and rs805305) genes were performed by TaqMan genotyping assays in 473 patients with MI and 447 healthy unrelated controls. Similar distribution of DDAH1 and DDAH2 polymorphisms was observed in MI patients and healthy controls. Under a recessive model adjusted for age, gender, and obesity, the rs805304 C allele was associated with decreased risk of MI (OR = 0.70, 95% CI = 0.51-0.96, P = 0.030). The effect of the polymorphisms on various cardiovascular risk factors was analyzed. Under a recessive model adjusted for age and gender, the DDAH2 rs805304 C allele was associated with decreased risk of obesity (OR = 0.35, 95% CI = 0.22-0.57, P = 0.001). The three DDAH2 polymorphisms were in strong linkage disequilibrium. Our results suggest that the rs805304 C allele was associated with decreased risk of MI and decreased risk of obesity.