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 lmol/L) alleles as compared to CC alleles (32.43 lmol/L) and CT alleles (30.54 lmol/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.

Effect of Methylenetetrahydrofolate Reductase (MTHFR) gene mutations and oxidative stress in silent brain infarction

“…There was no signi cant difference in other parameters in terms of genotype (Table 3). Some studies have stated that while variants of the A1298C gene do not affect homocysteine levels, some studies have been found [19,37,[43][44][45][46]. In studies, it has been stated that variants of the C677T gene increase the homocysteine level [45,19,36,37,47].…”

“…In severe MTHFR de ciency in which hyperhomocysteinemia and homocystinuria occur, clinical features such as peripheral neuropathy, growth retardation, hypotonia, stroke, and thrombosis are observed. Also, cases of mild MTHFR de ciency are quite common in the population, and it is claimed to be a risk factor especially in the formation of arterial diseases [18,12,19].…”

The Connotation of Variances in the Risk Predictors, Medications, Homocysteine, and Homocysteine Pathway Gene Polymorphisms with CVA/Stroke

“…The SNPs in folate pathway genes, rs1801133 and rs1801131 of the MTHFR gene, rs1805087 in MS, rs662 of PON1, and ACE gene (not in folate pathway) rs4646994 SNP have dissimilar association with stroke, as per literature. 11 12 13 14 The most extensively studied SNP in relation to stroke: MTHFR gene rs1801133 SNP is decisively associated with hyperhomocysteinemia, and is an additional risk enhancer for stroke. 36 None of the studied SNP, except for the rs1801133 of MTHFR (following regression analysis) was associated with stroke incidence in the current study.…”

“…[11][12][13] The rs1805087 SNP in methionine synthase (MS) gene although is related to thromboembolic phenomenon still it does not exhibit relation to stroke. 13 The stroke/CVA is high in patients with rs662 PON1 SNP and rs4646994 ACE SNP. 14,15 The medications used in hypertensive patients have disparate results in outcomes, with some drug regimens showing beneficial and others no role in stroke prevention.…”

“…The two significant single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T (rs1801133) and A1298C (rs1801131) are also strongly associated with risk of CVA/Stroke, with some studies exhibiting one SNP in favor of the other. 11 12 13 The rs1805087 SNP in methionine synthase ( MS ) gene although is related to thromboembolic phenomenon still it does not exhibit relation to stroke. 13 The stroke/CVA is high in patients with rs662 PON1 SNP and rs4646994 ACE SNP.…”