A common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its association with a haplotype in the Korean population

Abstract number: P0402

Park^* S., Yun^* T., Park^* S. R., Yoon^* S. S., Kim^* B. K., Kim† S. O., Hong† S. P., Chung† H. J., Yoo† W. D.

†R & D Center GeneMatrix, Republic of Korea ^*Seoul National University Hospital, Republic of Korea

The importance of hyperhomocysteinemia, neural-tube defects, birth defects, and vascular diseases has been the subject of intense investigations. The polymorphic methylenetetrahydrofolate reductase (MTHFR) mutations (C677T and A1298C) have been identified as a cause of mild hyperhomocysteinemia, especially in homozygotes for C677T, but also in compound heterozygotes for C677T/A1298C. The distribution of 677T is known to be worldwide, but its frequency in different populations varies extensively. We analyzed the frequency distribution of the previously described polymorphism C677T/A1298C in exon 4/7 and 23 additional variations of MTHFR gene from the dbSNP, OMIM and private databases in 96 Korean thrombosis patients receiving warfarin and healthy subjects. Genotyping carried out by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry identified 10 polymorphisms of minor allele frequency higher than 0.01 in MTHFR gene in 96 Korean individuals. The frequency of 677TT genotype was more frequent in patients than in control (25.0% vs. 12.5%). For analysis of a possible association between C677T allele and other polymorphisms, 24 haplotypes of the 10 variations in Korean population were built employing computational method (EM algorithm). The results showed that the 677T allele was remarkably associated with the other 9 common alleles including 31T in intron 6 and 1298 A in exon 7, and that two representative haplotypes which are made up of either all common alleles or all common alleles except 677 site constituted 77.8% of the total population. The presence of a high prevalence of allelic variants and/or haplotypes within MTHFR gene suggests compounding effects of the SNPs in the vascular diseases and thrombotic disorders.