Relationship between polymorphisms of folate metabolic enzymes 5, 10-methylenetetrahydrofolaye reductase gene 677 C>T, 5-methytetrahydrofolate homocysteine s-methltransferase gene 2756 A>G and susceptibility to endemic arsenicosis

Abstract

Objective To investigate the relationship between 5, 10-methylenetetrahydrofolate reductase(MTHFR) SNP rs1801133 (677 C>T), 5-methytetrahydrofolate homocysteine s-methltransferase (MTR) SNP rs1805087(2756 A>G) gene polymorphisms and susceptibility to endemic arsenic poisoning. Methods Case-control study design was employed to study 140 individuals who were identified as cases with arsenic induced skin lesions, and 157 individuals without skin lesions from the same villages were selected as controls in Inner Mongolia Autonomous Region, venous blood samples were collected, ethylenediamine tetraacetic acid disodium salt (EDTA) anticoagulant was added, MTHFR 677 C>T and MTR 2756 A>G genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-PFLP). Binary logistic analysis was used to analyze the affect of age, gender, period of residence, MTHFR 677 C>T and MTR 2756 A>G to endemic arsenicosis. Results MTHFR 677 C>T allele frequencies of C in case group and control group were 56.43% and 52.55%, respectively, and allele frequencies of T were 43.57% and 47.57%, respectively, the allele frequency between the two groups was not significantly different (χ2 = 0.90, P > 0.05); MTR 2756 A>G allele frequencies of A in case group and control group were 93.93% and 95.54%, respectively, and allele frequencies of G were 6.07% and 4.46%, respectively, the allele frequency between the two groups was not significantly different (χ2 = 0.84, P > 0.05). In MTHFR 677 C>T, CC genetypes in case group and control group were 22.86% and 18.47%, respectively; CT genotypes were 67.14% and 67.52%, respectively; TT genotypes were 10.00% and 14.01%, respectively. The differences between hybrid type CT, mutant TT, combined hybrid type CT with mutant TT and wild type CC were not significantly different (χ2 = 0.56, 0.81, 0.87, all P > 0.05). In MTR 2756 A>G, AA genetypes in case group and control group were 87.86% and 91.72, respectively; AG genotypes were 12.14% and 7.64%, GG genotypes were 0.00% and 0.64%, respectively. The differences between hybrid type AG, mutant type GG, combined hybrid type AG with mutant GG and wild type AA were not significantly different (χ2 = 1.65, 1.35, 1.22, all P > 0.05). The group of over 60 years old had higher risk of endemic arsenic poisoning with 2.78 times higher than the group of less 40 years old, the group of over 40 years old had higher risk of endemic arsenic poisoning with 1.85 times higher than the group of less than 40 years, and the difference was significant [odd ratio (OR) = 2.78, 1.85, P 0.05). There was no significant difference in prevalence between wild type CC and hybrid type CT, mutation type TT in MTHFR 677 C>T, respectively (OR = 1.53, 1.63, all P > 0.05). There was no significant difference in prevalence between wild type AA and hybrid type AG, mutation type GG in MTR 2756 A>G, respectively (OR = 1.53, 1.63, all P > 0.05). Conclusion This study does not find a positive correlation between MTHFR 677 C>T and MTR 2756 A>G polymorphism in endemic arsenicosis. Key words: Arsenic poisoning; 5, 10-methylenetetrahydrofolate reductase; 5-methytetrahydrofolate homocysteine s-methyltransferas; Polymorphism; Susceptibility