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

<div><p>Aim</p><p>To explore the role of the <i>ACE</i> gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels.</p><p>Methods</p><p>Nine <i>ACE</i> 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. <i>ACE</i> serum levels were determined in selected individuals according to different haplotypes.</p><p>Results</p><p>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 (<i>AAGCA</i>), H2 (<i>GGATG</i>), H3 (<i>AGATG</i>), and H4 (<i>AGACA</i>). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, <i>P</i> = 0.023 and OR = 1.41, <i>P</i> = 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; <i>P</i> = 0.002 and OR = 2.09; <i>P</i> = 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 (<i>P</i> = 0.0048).</p><p>Conclusion</p><p>The results suggest that single nucleotide polymorphisms and the “<i>GGATG</i>” haplotype of the <i>ACE</i> gene are associated with the development of hypertension and with increased ACE enzyme levels.</p></div

Demographic characteristic of the population.

<p>Data are expressed as means ± SD, log-transformed values were used for statistical analysis.</p>*<p>P values were computed using ANOVA for continuous variables and Pearson’s Chi-square test for categorical values.</p><p>CAD: coronary artery disease; SA: subclinical atherosclerosis.</p

Association of the (C > T) rs1412444 polymorphism with coronary risk factors.

<p>All association were tested using logistic regression adjusted for age, gender, BMI, and medication when appropriate. (n) Represents the number of cases with each trait.</p><p>RAF: risk allele frequency.</p

Association of the (C > T) rs2246833 polymorphism with coronary risk factors.

<p>All association were tested using logistic regression adjusted for age, gender, BMI, and medication when appropriate. (n) Represents the number of cases with each trait.</p><p>RAF: risk allele frequency.</p

Comparison of biochemical parameters in individuals with premature coronary artery disease, subclinical atherosclerosis, and controls.

<p>Data are expressed as means ± SD, log-transformed values were used for statistical analysis.</p>*<p>P values were computed using ANOVA for continuous variables and Pearson’s Chi-square test for categorical values.</p><p>CAD: coronary artery disease; SA: subclinical atherosclerosis.</p

MOESM1 of Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus

Additional file 1: Table S1. Combined association of fatty liver and markers of adipose tissue dysfunction with the risk of IFG and nT2D in the paired-matched subpopulation

The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population

<div><p>Abstract We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.</p></div

HLA Class I and II Blocks Are Associated to Susceptibility, Clinical Subtypes and Autoantibodies in Mexican Systemic Sclerosis (SSc) Patients

<div><p>Introduction</p><p>Human leukocyte antigen (HLA) polymorphism studies in Systemic Sclerosis (SSc) have yielded variable results. These studies need to consider the genetic admixture of the studied population. Here we used our previously reported definition of genetic admixture of Mexicans using HLA class I and II DNA blocks to map genetic susceptibility to develop SSc and its complications.</p><p>Methods</p><p>We included 159 patients from a cohort of Mexican Mestizo SSc patients. We performed clinical evaluation, obtained SSc-associated antibodies, and determined HLA class I and class II alleles using sequence-based, high-resolution techniques to evaluate the contribution of these genes to SSc susceptibility, their correlation with the clinical and autoantibody profile and the prevalence of Amerindian, Caucasian and African alleles, blocks and haplotypes in this population.</p><p>Results</p><p>Our study revealed that class I block HLA-C*12:03-B*18:01 was important to map susceptibility to diffuse cutaneous (dc) SSc, HLA-C*07:01-B*08:01 block to map the susceptibility role of HLA-B*08:01 to develop SSc, and the C*07:02-B*39:05 and C*07:02-B*39:06 blocks to map the protective role of C*07:02 in SSc. We also confirmed previous associations of HLA-DRB1*11:04 and –DRB1*01 to susceptibility to develop SSc. Importantly, we mapped the protective role of DQB1*03:01 using three Amerindian blocks. We also found a significant association for the presence of anti-Topoisomerase I antibody with HLA-DQB1*04:02, present in an Amerindian block (DRB1*08:02-DQB1*04:02), and we found several alleles associated to internal organ damage. The admixture estimations revealed a lower proportion of the Amerindian genetic component among SSc patients.</p><p>Conclusion</p><p>This is the first report of the diversity of HLA class I and II alleles and haplotypes Mexican patients with SSc. Our findings suggest that HLA class I and class II genes contribute to the protection and susceptibility to develop SSc and its different clinical presentations as well as different autoantibody profiles in Mexicans.</p></div

Principal component analysis (PCA) plot reveals a close genetic relationship of Mexican admixed SSc patients and healthy controls (HC) from Mexico City to Native American groups.

<p>Native American populations are represented in the upper left of the graphic and Caucasian components in the right bottom area of the graphic. Amerindian components are represented in the left bottom area. Red and blue dots represent difusse and limited SSc patients respectively and the total group in represented in green. The different populations included in the PCA analysis were: Ire: Ireland, Eng: England, Ger: Germany, Aus: Austria; Spa: Spain, Ita: Italy, UK: United Kingdom, Fra: France, Azo: Azores, Sao: São Tomé Island, Cam: Cameroon, Mal: Mali, Zam: Zambia, KLu: Luo from Kenia, KNa: Nandi from Kenia, Sen: Senegal, Gui: Guinea Bissau, Tar: Tarahumara, Gil: Native Americans from Gila River, Yup: Yu’pik from Alaska, Mit: Mixtec from Oaxaca, Zap: Zapotec from Oaxaca, Mix: Mixe from Oaxaca, Ser: Seri from Sonora, Nav: Navajo from New Mexico, HC: “Mexican Admixed controls” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126727#pone.0126727.ref026" target="_blank">26</a>].</p

Demographic data and organ damage according to the modified Medsger’s Severity Scale.

<p>dcSSc: diffuse cutaneous systemic sclerosis, lcSSc: limited cutaneous systemic sclerosis, ILD: interstitial lung disease; PAH: pulmonary arterial hypertension.</p><p>Demographic data and organ damage according to the modified Medsger’s Severity Scale.</p