Association of Genetic Variants with Hyperhomocysteinemia in Indian Patients with Thrombosis

Abstract

Hyperhomocysteinemia known to be associated with increased thrombotic tendency has been considered as a risk factor for coronary artery disease, atherosclerosis, venous thrombosis, and stroke. There are three main genes MTHFR, cystathionine beta-synthase (CBS) and methionine synthase (MS) and it's genetic variant that are known to influence the homocysteine metabolism leading to hyperhomocysteinemia. There is scarcity of Indian data on hyperhomocysteinemia and genetics variants in patients with thrombosis. Hence the objective of present study was to determine MTHFR, CBS, and MS genetic variants in thrombosis patients from Indian population. Genetic variant analysis was performed on thrombosis patients to detect MTHFR C677T (rs1801133), MTHFR A1298C (rs1801131), MS A2756G (rs1805087) and CBS T833C (rs5742905) mutations. The mutant allele frequencies of MTHFR 677T, MTHFR 1298C, MS2756G and CBS 833C were observed to be 16.1%, 37.5%, 34.1% and 5.8% respectively. MTHFR 677TT genotype was observed to be significantly associated with elevated homocysteine (Hcy) levels (64.65 μmol/L) alleles as compared to CC alleles (32.43 μmol/L) and CT alleles (30.54 μmol/L). MTHFR A1298C, MS A2756G and CBS T833C genotypes did not showed significant association with higher Hcy levels. Thus, in Indian patients with thrombosis only MTHFR T677T genotype was observed to be significantly associated with hyperhomocysteinemia.

Keywords: Hyperhomocysteinemia; Indians; MTHFR mutants; Thrombosis.

Fig. 1

Allelic distribution and homocysteine levels. a C677T alleles and b A1298C alleles

Fig. 2

Allelic distribution and homocysteine levels in a patients with DVT and b patients with brain thrombosis

Fig. 3

Homocysteine levels and MSA2756G alleles and CBS T833C alleles

Fig. 4

MTHFR haplotypes and homocysteine levels

Fig. 5

Distribution of MTHFR haplotypes in patients with different homocysteine levels. a Hcy levels 0–10 μmol/L (n = 28); b Hcy levels 10–15 μmol/L (n = 23); c Hcy levels 15–30 μmol/L (n = 34); d Hcy levels >30 μmol/L (n = 44)