Sequence Variation of the Methylene Tetrahydrofolate Reductase Gene (677C>T and 1298 A>C) and Traditional Risk Factors in a South Indian Population

Abstract

Methylene tetrahydrofolate reductase (MTHFR) plays a significant role in the metabolism of methionine. MTHFR deficiency is an autosomal recessive trait that could be a significant risk factor for a number of defects, for example, vascular events, due to lower dietary folate intake among South Indians. To find the incidence of 677 C>T and 1298 A>C in MTHFR gene single nucleotide polymorphisms (SNPs) among the south Indian population, polymerase chain reaction and restriction fragment length polymorphism were employed among 152 patients with myocardial infarction and 167 controls. The MTHFR 677CT genotype was found among 35 (22.4%) cases and 08 (4.8%) controls, the MTHFR 677CC allele was found among 115 (73.7%) cases and 159 (94.6%) controls. Also, the analysis of the MTHFR 1298A>C SNP identified the MTHFR 1298CC genotype among 16 (10.3%) cases and 01 (0.6%) control, the MTHFR 1298AC genotype was found in 56 (35.9%) cases and 27 (16.2%) controls, and the MTHFR 1298AA genotype was observed in 80 (51.3%) cases and 139 (82.6%) controls. The C vs. A allele also showed significantly higher frequency among the patients in comparison with the controls (p<0.0001). The results of this study indicate that the MTHFR A1298C SNP is more prevalent among south Indians compared with the MTHFR C677T SNP, suggesting a possible role of MTHFR A1298C in the pathogenesis of heart diseases.

Methylene tetrahydrofolate reductase polymorphisms and homocysteine level in heart defects

“…14 Earlier studies have reported inconsistent results regarding the association between the 677C>T and 1298A>C polymorphisms and congenital cardiac defects. [9][10][11]15 In our previous studies, we failed to demonstrate a relationship between neural tube defects and MTHFR polymorphisms in a Turkish population, despite the high prevalence of the condition. 16 The present study was conducted to evaluate the polymorphisms 677C>T and 1298A>C in a group of Turkish children with various types of congenital heart defects.…”

“…Earlier studies have reported inconsistent results regarding the association between the 677C>T and 1298A>C polymorphisms and congenital cardiac defects …”

“…These methylation‐dependent reactions and substances are vital for normal tissue growth and maturation. Previous reports have related 677C>T polymorphism homozygosity to increased risk for some defects, such as neural tube defects and oral clefts . A second polymorphism involving alanine‐to‐cytosine nucleotide substitution (1298A>C polymorphism) in the MTHFR gene has also been reported to be related to hyperhomocysteinemia .…”

“…Previous reports have related 677C>T polymorphism homozygosity to increased risk for some defects, such as neural tube defects and oral clefts. [9][10][11] A second polymorphism involving alanine-tocytosine nucleotide substitution (1298A>C polymorphism) in the MTHFR gene has also been reported to be related to hyperhomocysteinemia. 12 In another study, homozygosity for 1298A>C was related to increased risk for early onset coronary artery disease independent of homocysteine level.…”

No association of the MTHFR gene A1298C polymorphism with the risk of prostate cancer: A meta-analysis

“…Recently, SNPs have been used as a tool for predicting diseases (12) in addition to carcinogenesis (13,14). The MTHFR gene A1298C polymorphism has been implicated in several diseases (15,16), including various types of cancer (17,18), and has been investigated in relation to the risk of PC but with inconclusive results (19)(20)(21)(22)(23)(24)(25)(26)(27). Among the nine eligible casecontrol studies, three considered the MTHFR gene A1298C polymorphism as a genetic marker for PC (19,24,26), while six reported negative associations between the two (20)(21)(22)(23)25,27).…”