Methylenetetrahydrofolate Reductase (MTHFR) C677T and A1298C Polymorphisms in Georgian Females with Hypothyroidism.

Elene Abzianidze,Eka Kvaratskhelia,Sandro Surmava,Merab Kvintradze,Ketevan Asatiani,Tamar Kvaratskhelia

doi:10.1055/s-0040-1714091

Abstract

The aim of this study was to investigate the frequency of methylenetetrahydrofolate reductase ( MTHFR) gene polymorphisms in Georgian females with hypothyroidism. Thirty-four patients and 29 healthy individuals were recruited in this study. Polymerase chain reaction-restriction fragment length polymorphism analyses were used for genotyping of MTHFR polymorphisms. The results of this study suggest that the MTHFR C677T variant was significantly associated with hypothyroidism. In addition, in individuals with T allele risk of hypothyroidism significantly increased. Combination of CT/AA genotypes was more prevalent in the hypothyroid patients than in the control group. Thus, C677T polymorphism could be a possible genetic factor contributing to the pathophysiology of hypothyroidism, possibly through hyperhomocysteinemia.

Highlights

Methylenetetrahydrofolate reductase (MTHFR) is the trifunctional enzyme catalyzing conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which in turn is the major circulatory form of the folate in the blood and the co-substrate for homocysteine (Hcy) remethylation to methionine.[1]
The distribution of C677T and A1298C polymorphism allelic, genotype and combined genotype frequencies in patients with hypothyroidism and healthy controls is shown in ►Table 3
We evaluated all possible genotype combinations according to C677T and A1298C polymorphisms in MTHFR—677CC/1298AA, 677CC/ 1298AC, 677CC/1298CC, 677CT/1298AA, 677CT/1298AC, 677CT/1298CC, 677TT/1298AA, 677TT/1298AC, and 677TT/ 1298CC; the frequencies in the case and control groups, respectively, were 32.4, 8.8, 5.9, 35.3, 8.8, 0, 8.8, 0, 0% and 69, 6.9, 10.3, 6.9, 6.9, 0, 0, 0, and 0%

Summary

Introduction

Methylenetetrahydrofolate reductase (MTHFR) is the trifunctional enzyme catalyzing conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which in turn is the major circulatory form of the folate in the blood and the co-substrate for homocysteine (Hcy) remethylation to methionine.[1]. A common C677T polymorphism at exon 4 causes an amino acid substitution at position 222 from alanine to valine (A222V), making the enzyme thermolabile. Its decreased activity causes the development of mild hyperhomocysteinemia.[6,7]. Another common SNP is an A to C change in position 1298 (A1298C) at exon 7 causing a glutamate to alanine substitution on the 429th position, resulting in decreased MTHFR activity, which is not associated with thermolability of an enzyme. Decreased MTHFR activity is more pronounced in the homozygous state than the heterozygous, and it does not appear to cause hyperhomocysteinemia in either genotype, but its combination with the C677T polymorphism—compound heterozygosity—results in significant elevation of plasma Hcy, even more severe than in 677TT individuals.[8–10]

Objectives

Methods

Results

Conclusion