The MT2A gene polymorphisms and risk factors for CVD in healthy Thais according to smoking status

Abstract

Cardiovascular diseases (CVD) represent the major global health problem. The CVD risk factors include smoking, hypertension, diabetes, obesity, and dyslipidemia. Cigarette smoke contains toxic substances and heavy metals such as cadmium that can induce body oxidative stress. Metallothionein (MT), an important metal binding protein, plays key roles in the homeostasis and transportation of essential heavy metals such as zinc and copper, scavenging of free radicals, and detoxifying of toxic heavy metal like cadmium. The most abundant MT isoform found in human tissues is MT2A. Mutations at core promoter region of MT2A gene can affect the gene expression. Moreover, mutations at 3'UTR affect mRNA stability, translation process and cellular localization. The aim of present study was to investigate the polymorphisms of MT2A gene and CVD risk factors in Thai smokers and never-smokers. The study was conducted in a total of 222 Thai individuals consisting of 157 never-smokers, 17 former-smokers, and 48 current-smokers. The MT2A-5A/G and +838C/G gene polymorphisms were investigated by PCR-RFLP technique. The respective minor allele frequencies of MT2A-5G and +838C were 2.7 and 20.0%. MT2A-5A/G gene polymorphism was related to serum malondialdehyde (MDA) level and hypertension. The MDA levels in all subjects, never-smokers, and former-smokers with AG genotype were significantly higher than in those with AA genotype. Systolic blood pressure (SBP) and the prevalence of hypertension were also significantly higher in all subjects and never-smokers with AG genotype than in those with AA genotype (P = 0.003 and P = 0.019 respectively). For the MT2A +838C/G, the prevalence of dyslipidemia in current-smokers with GG genotype was higher than in those with GC+CC genotype (P = 0.040). These findings suggest that MT2A gene polymorphism may have application on assessment for risk of oxidative stress, hypertension, and dyslipidemia; all of these are known as risk factors for CVD.