The variant rs8048002 T>C in intron 3 of the MHC2TA gene is associated with risk of developing acute coronary syndrome.

Recently, an intronic single nucleotide polymorphism (rs8048002) in the MHC class II transactivator gene (MHC2TA) was shown to be associated with increased susceptibility to several inflammatory diseases. The aim of the present study was to test for an association between this MHC2TA gene polymorphism and susceptibility to the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. The single nucleotide polymorphism (rs8048002) of the MHC2TA gene was analyzed by 5' exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 456 healthy controls. The C allele and TC genotype were associated with risk of developing ACS (OR=4.55, pC=6×10(-4) and OR=4.41, pC=1.5×10(-3), respectively). Multiple logistic analysis was used for estimate risk between ACS patients and controls adjusted by cardiovascular risk factors (gender, age, hypertension, dyslipidemia, smoking, diabetes, body mass index and alcohol consumption). In this analysis, the TC+CC genotypes were significantly associated with increased risk of ACS as compared to TT genotype (OR=4.56, pC=0.004). In summary, our data suggest that the MHC2TA rs8048002 C>T gene polymorphism plays an important role in the risk of developing ACS.

Haplotypes of the angiotensin-converting enzyme (ACE) gene are associated with coronary artery disease but not with restenosis after coronary stenting.

The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population.

The aim of the present study was to establish the gene frequency of six polymorphisms of the ABCB1, CYP3A5, CYP2C19, and P2RY12 genes in a population resident of Mexico City. The proteins encoded by these genes have been associated with the absorption, and biotransformation of clopidogrel. The ABCB1 T3435C, CYP3A5 V3 A6986G, P2RY12 G52T, P2RY12 C34T, CYP2C19 V2 and V3 (positions G681A and G636A, respectively), polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 269 healthy unrelated Mexican Mestizo individuals. The CYP2C19 V3 G636A polymorphism was not detected in the Mexican Mestizos population. However, the studied population presented significant differences (P < 0.05) in the distribution of the T3435C, A6986G, G681A, G52T and C34T polymorphisms when compared to reported frequencies of Amerindian of South America, Caucasian, Asian, and African populations. In summary, the distribution of the ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms distinguishes to the Mexican Mestizos population from other ethnic groups.

The MHC2TA gene polymorphisms are not associated with restenosis after coronary stenting in Mexican patients.

OBJECTIVE: The aim of this study was to test for association between MHC2TA gene polymorphisms and risk for restenosis after coronary stent placement in a group of Mexican patients. METHODS: The MHC2TA-168A>G (rs3087456), 1614C>G (rs4774), and 2536G>A (rs2229320) single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays in a group of 202 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. RESULTS: The results obtained in this study showed that the frequency of the three polymorphisms studied was similar in patients with and without restenosis. Univariate analysis showed that the use of drug-eluting stent (DES) reduces the risk of developing restenosis (p<0.001, OR=0.26). In contrast, the diameter<2.5mm of the stent and bifurcations increased the risk of developing restenosis (p=0.049, OR=1.74 and p=0.041, OR=1.8). CONCLUSION: The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement.

Interleukin 1 ß (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 ß (IL-1ß) seems to have a central role because of its immunoregulatory and proinflammatory activities. GOAL: To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. STUDY: Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. RESULTS: We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). CONCLUSIONS: IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

The T>A (rs11646213) gene polymorphism of cadherin-13 (CDH13) gene is associated with decreased risk of developing hypertension in Mexican population.

Hypertension is a major public health problem affecting about 30% of the adult population and is associated with an increased risk of developing metabolic and cardiovascular disease. Recent reports have shown that the T-cadherin receptor characteristically expressed on endothelial and vascular smooth muscle cells is involved in hypertension. The aim of the present study was to evaluate the role of cadherin-13 (CDH13) gene polymorphisms as susceptibility markers for hypertension in Mexican population. Six CDH13 polymorphisms (rs11646213, rs11646411, rs6563943, rs3096277, rs3784990 and rs254340) were genotyped by 5' exonuclease TaqMan assays in a group of 644 hypertensive and 765 non-hypertensive individuals. Under co-dominant, recessive, and additive models, the CDH13 T>A (rs11646213) polymorphism was associated with decreased risk of developing hypertension when compared to non-hypertensive individuals (OR=0.61, 95% CI: 0.42-0.89, Pco-dom=0.019; OR=0.63, 95% CI: 0.46-0.87, Pres=0.005; OR=0.80, 95% CI: 0.66-0.96, Padd=0.016, respectively). All models were adjusted by gender, age, body index mass, type II diabetes mellitus, alcohol consumption, dyslipidemia and smoking habit. Linkage disequilibrium analysis showed one haplotype (TCACGG) with decreased frequency in hypertensive when compared to non-hypertensive individuals (OR=0.52, 95% CI: 0.33-0.82, P=0.0053). In summary, our data suggests that the CDH13 T>A (rs11646213) polymorphism is associated with decreased risk of developing hypertension in the Mexican population. In addition, it was possible to distinguish one haplotype associated with decreased risk and two for increased risk of develop hypertension.

The (G>A) rs11573191 polymorphism of PLA2G5 gene is associated with premature coronary artery disease in the Mexican Mestizo population: the genetics of atherosclerotic disease Mexican study.

Coronary artery disease (CAD) is a multifactorial disorder that results from an excessive inflammatory response. Secretory phospholipase A2-V (sPLA2-V) encoded by PLA2G5 gene promotes diverse proinflammatory processes. The aim of the present study was to analyze if PLA2G5 gene polymorphisms are associated with premature CAD. Three PLA2G5 polymorphisms (rs11573187, rs2148911, and rs11573191) were analyzed in 707 patients with premature CAD and 749 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Under dominant, recessive, and additive models, the rs11573191 polymorphism was associated with increased risk of premature CAD (OR = 1.51, P(dom) = 3.5 × 10(-3); OR = 2.95, P(rec) = 0.023; OR = 1.51, P(add) = 1.2 × 10(-3)). According to the informatics software, this polymorphism had a functional effect modifying the affinity of the sequence by the MZF1 transcription factor. PLA2G5 polymorphisms were in linkage disequilibrium and the CGA haplotype was associated with increased risk of premature CAD (OR = 1.49, P = 0.0023) and with hypertension in these patients (OR = 1.75, P = 0.0072). Our results demonstrate the association of the PLA2G5 rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension.

Distribution of the IL-1RN, IL-6, IL-10, INF-γ, and TNF-α Gene Polymorphisms in the Mexican Population.

BACKGROUND: Cytokines are a group of polypeptides with an important role in the inflammatory response. It has been suggested that certain polymorphisms located in several cytokine genes are associated with different diseases. The aim of the present study was to establish the gene frequency of 13 polymorphisms of the IL-1RN, IL-6, IL-10, INF-γ, and TNF-α genes in a Mexican population. These polymorphisms have been reported in several populations, with important variation in frequency according to the studied population. METHODS: Thirteen polymorphisms (rs419598, rs315951, rs2234663, rs3811058, rs1800796, rs2069827, rs1800896, rs1800871, rs1800872, rs1800629, rs2069709, rs2069710, and rs361525) were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 248 healthy unrelated Mexican individuals. RESULTS: The results obtained showed that the studied Mexican population presents significant differences (p<0.05) in the distribution of the IL1RN (rs419598, rs315951, and and rs2234663), IL1F10 (rs3811058), IL6 (rs1800796, rs2069827), IL10 (rs1800896, rs1800871, and rs1800872), and TNF-α (rs1800629) polymorphisms when compared to Caucasian, Asian, and African populations. CONCLUSIONS: In summary, the distribution of the IL-1RN, IL-6, IL-10, and TNF-α cytokine gene polymorphisms distinguishes the studied Mexican population from other groups. Since the alleles of these cytokines are associated with the development of several inflammatory diseases, knowledge of the distribution of these alleles in the studied Mexican population could be helpful to understand their true role as a genetic susceptibility marker in this population.

[Genetic and genomic studies in the hypertension: an actualization of the genomic studies]. / Genética y genómica de la hipertensión arterial: una actualización.

The arterial hypertension is considered to be the main risk factor for myocardial infarction, heart failure, ventricular arrhythmias, kidney failure, blindness and other diseases. Arterial hypertension is a multifactorial disease derived from environmental, genetic, gender and ethnic factors. In recent years, the World Health Organization estimated that approximately 17.5 million of deaths were due to cardiovascular diseases worldwide and that this pathology will become the leading cause of death in the next decade. Data from the National Survey of Mexican Ministry of Health (2006), reported approximately 17 million hypertensive adults, equivalent to a prevalence of 30.8% among Mexican population. As a consequence, hypertension represents the leading cause of morbidity from 2000 to 2005 and is increasing in recent years. However, studies have failed to clearly identify the molecular and genetic mechanisms of this pathology so far. Nevertheless, using the new technologies for analysis of variants in the genome, several genes in different loci that confer susceptibility to develop hypertension have been identified. In this review we compared the different studies in genetics and genomics of the hypertension that have been made worldwide and in Mexico, with the aim of identifying important genes involved in susceptibility to the development of this pathology.

The MHC2TA gene polymorphisms are not associated with restenosis after coronary stenting in Mexican patients / Los polimorfismos del gen MHC2TA no se asocian con la reestenosis después del implante de stent coronario en pacientes mexicanos

Objective: The aim of this study was to test for association between MHC2TA gene polymorphisms and risk for restenosis after coronary stent placement in a group of Mexican patients. Methods: The MHC2TA-168A>G (rs3087456), 1614C>G (rs4774), and 2536G>A (rs2229320) single nucleotide polymorphisms were genotyped using 5' exonuclease TaqMan genotyping assays in a group of 202 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Results: The results obtained in this study showed that the frequency of the three polymorphisms studied was similar in patients with and without restenosis. Univariate analysis showed that the use of drug-eluting stent (DES) reduces the risk of developing restenosis (p < 0.001, OR = 0.26). In contrast, the diameter< 2.5 mm of the stent and bifurcations increased the risk of developing restenosis (p = 0.049, OR = 1.74 and p = 0.041, OR = 1.8). Conclusion: The present study suggests that the MHC2TA polymorphisms are not involved in the risk of developing restenosis after coronary stent placement.

Objetivo: El propósito de este estudio fue evaluar la asociación de los polimorfismos del gen MHC2TA y el riesgo de desarrollar reestenosis, después del implante de stent coronario en un grupo de pacientes mexicanos. Métodos: Los polimorfismos de un solo nucleótido MHC2TA-168A>G (rs3087456), 1614C>G (rs4774) y 2536G>A (rs2229320), se determinaron en un grupo de 202 pacientes tratados con stent coronario. Los polimorfismos fueron evaluados utilizando ensayos de genotipificacion Taq-Man 5' exonucleasa. El procedimiento basal y la búsqueda de predictores de reestenosis fueron analizados por medio de angiografía coronaria, y seguimiento angiográfico con el fin de detectar reestenosis binaria. Resultados: Los resultados obtenidos en este estudio mostraron que la distribución génica de los tres polimorfismos estudiados fue muy similar, en pacientes con o sin reestenosis. Sin embargo, el análisis univariado mostró que el uso de los stent medicados reducen el riesgo de desarrollar reestenosis (p < 0.001, OR = 0.26). En contraste, con las bifurcaciones y el diámetro < 2.5 mm del stent que se incrementa el riesgo de desarrollar reestenosis (p = 0.049, OR = 1.74 y p = 0.041, OR = 1.8). Conclusión: El presente estudio sugiere que los polimorfismos del gen MHC2TA no están asociados con el riesgo de desarrollar reestenosis, después del implante de stent coronario.

Genética y genómica de la hipertensión arterial: una actualización / Genetic and genomic studies in the hypertension: an actualization

La hipertensión arterial es considerada la principal causa de riesgo para el desarrollo de infarto agudo al miocardio, falla cardiaca, arritmia ventricular, nefropatía, ceguera, entre otras. La hipertensión arterial es una enfermedad multifactorial en la que participan factores ambientales, genéticos e intrínsecos como raza y género. La Organización Mundial de la Salud ha estimado que la prevalencia de la hipertensión se incrementará drásticamente, de modo que en la próxima década será la primera causa de muerte a nivel mundial, debido al elevado número de muertes (17.5 millones) por enfermedades cardiovasculares registradas a nivel mundial. No obstante, los datos publicados en la Encuesta Nacional de la Secretaría de Salud en 2006, señalan aproximadamente 17 millones de hipertensos en población adulta y una prevalencia de 30.8%, cifra que indica que la hipertensión arterial aumentó su morbilidad del año 2000 al 2005. Sin embargo, poco se ha logrado en la comprensión de los mecanismos moleculares y genéticos involucrados en el desarrollo de esta patología y en consecuencia su prevalencia sigue aumentando drásticamente. Con el uso de las nuevas tecnologías para el análisis de las variantes en el genoma, se han identificado algunos genes en diferentes loci que confieren susceptibilidad al desarrollo de hipertensión arterial. La finalidad de esta revisión es hacer una comparación entre los diferentes estudios en genética y genómica relacionados con esta patología a nivel mundial y en nuestro país, con la finalidad de identificar genes clave que participen en la susceptibilidad al desarrollo de la hipertensión arterial.

The arterial hypertension is considered to be the main risk factor for myocardial infarction, heart failure, ventricular arrhythmias, kidney failure, blindness and other diseases. Arterial hypertension is a multifactorial disease derived from environmental, genetic, gender and ethnic factors. In recent years, the World Health Organization estimated that approximately 17.5 million of deaths were due to cardiovascular diseases worldwide and that this pathology will become the leading cause of death in the next decade. Data from the National Survey of Mexican Ministry of Health (2006), reported approximately 17 million hypertensive adults, equivalent to a prevalence of 30.8% among Mexican population. As a consequence, hypertension represents the leading cause of morbidity from 2000 to 2005 and is increasing in recent years. However, studies have failed to clearly identify the molecular and genetic mechanisms of this pathology so far. Nevertheless, using the new technologies for analysis of variants in the genome, several genes in different loci that confer susceptibility to develop hypertension have been identified. In this review we compared the different studies in genetics and genomics of the hypertension that have been made worldwide and in Mexico, with the aim of identifying important genes involved in susceptibility to the development of this pathology.