Analysis of Polymorphisms in Genes (AGT, MTHFR, GPIIIa, and GSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México

323 Disease Markers 28 (2010) 323–331 DOI 10.3233/DMA-2010-0712 IOS Press Analysis of polymorphisms in genes (AGT, MTHFR, GPIIIa, and GSTP1) associated with hypertension, thrombophilia and oxidative stress in Mestizo and Amerindian populations of México Rocio Juárez-Velázqueza,b, Patricia Cantoc , Thelma Canto-Cetinad , Hector Rangel-Villalobose, Haydee Rosas-Vargas a, Maricela Rodrı́guezf , Samuel Canizales-Quinteros g, Ana Claudia Velázquez Wong a, Rosa Marı́a Ordoñez-Razoa, Guadalupe Vilchis-Dorantes h and Ramón Mauricio Coral-Vázquezi,∗ a Unidad de Investigaci ón Médica en Genética Humana, Hospital de Pediatrı́a, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, M éxico, D.F., México b Present adress: Laboratorio de Cultivo de Tejidos, Departamento de Investigaci ón en Genética Humana. Instituto Nacional de Pediatrı́a, México, D.F., México c División de Investigaci ón Biomédica, Subdirecci ón de Enseñanza e Investigaci ón, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, M éxico, D.F., México d Laboratorio de Biologı́a de la Reproducci ón, Departamento de Salud Reproductiva y Gen ética, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, M érida Yucatán, México e Laboratorio de Gen ética Molecular (CUCiénega-U de G), Departamento de Ciencias M édicas y de la Vida, Centro Universitario de la Ciénega, Universidad de Guadalajara, Ocotl án, Jalisco, Mexico f Unidad de Investigaci ón Médica en Nutrición. Centro Médico Nacional Siglo XXI, Coordinaci ón de Investigaci ón en Salud, Instituto Mexicano del Seguro Social, M éxico, D.F., México g Unidad de Biologı́a Molecular y Medicina Gen ómica, Instituto Nacional de Ciencias M édicas y Nutrición “Salvador Zubirán”, México, D.F., México h Laboratorio de Gen ética Forense, Dirección de la Coordinaci ón General de Servicios Periciales, Procuradurı́a General de la Republica (PGR), Mexico City, Mexico i Laboratorio Multidisciplinario, Secci ón de Posgrado, Escuela Superior de Medicina, Instituto Polit écnico Nacional, México, DF., México & División de Medicina Gen ómica, Subdirecci ón de Enseñanza e Investigaci ón, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, México, D.F., México Abstract. Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenetetrahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymor- ∗ Corresponding author: Dr. Ramón Mauricio Coral Vázquez, Laboratorio Multidisciplinario, Escuela Superior de Medicina, Plan de San Luis y Dı́az Mirón s/n, Col. Casco de Santo Tomas, México. Tel.: +5255 57296300 ext. 16820; Fax: +5255 57296300 ext 16820; E-mail: . ISSN 0278-0240/10/$27.50  2010 – IOS Press and the authors. All rights reserved 324 R. Juárez-Velázquez et al. / Analysis of polymorphisms in genes (AGT, MTHFR, GPIIIa, and GSTP1) associated phisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using χ2 tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups. Keywords: Gene polymorphisms, AGT, GPIIIa, GSTP1, MTHFR, Mexican populations 1. Introduction Several epidemiological and clinical studies have reported associations between polymorphisms of various genes related to hypertension, thrombophilia, and oxidative stress with development of cardiovascular and cerebrovascular diseases. Among these genes are angiotensinogen (AGT) (MIM 106150) [1], glycoprotein IIIa (GPIIIa) (MIM 173470) [2], 5,10 methylenetetrahydrofolate reductase (MTHFR) (MIM 607093) [3], and glutathione S-transferase P1 (GSTP1) (MIM 134660) [4]. However, other studies have shown no evidence of association between these polymorphisms and risk of these diseases [1,5,6]. Approximately 30% to 40% of the population variability in blood pressure is genetically determined [7]. The importance of the renin-angiotensin system for maintenance of normal cardiovascular homeostasis is well established [8]. It has been suggested that individuals with a p.M235T (c.704C>T) polymorphism in the AGT gene in the homozygous TT state have increased plasma angiotensinogen levels and a corresponding increase in risk of hypertension [9]. Likewise, it was demonstrated that moderate hyperhomocysteinemia is considered as an independent risk factor for ischemic cardiovascular disease [10]. The genetic basis of this disease may be due to a polymorphism in the MTHFR gene (p.A222V, c.677C>T) where homozygosity for the C-677T substitution results in reduced MTHFR enzyme activity and subsequently elevated homocysteine concentrations of ∼20% [11]. GPIIIa is a thrombophilic gene involved in the regulation of vascular thrombosis. The GPIIb/GPIIIa complex mediates platelet aggregation by acting as a receptor for fibrinogen. This complex also acts as a receptor for von Willebrand factor and fibronectin [12]. The polymorphism c.98C>T in this gene causes a p.L33P substitution and the existence of two antigeni- cally distinct forms of the mature GPIIb/IIIa antigen on platelets [13]. This variant itself has been associated with risk of premature acute coronary syndromes and stroke in young Caucasian women [14]. In addition, oxidative stress is thought to play an important role in the pathophysiology of hypertension, although this statement lies within the context of the development of preeclampsia [15]. It has been hypothesized that reduced levels of GSTP1 due to the the lower activity of the GSTP1 (p.I105V, c.313A>G) allele in this syndrome may be an indicator of decreased capacity of the GST detoxification system and may cause a prolonged exposure to reactive by-products, which may contribute to maternal endothelial dysfunction [15,16]. It has been observed that diverse ge (...truncated)