Homocysteine and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Tunisian patients with severe coronary artery disease

Abstract

Elevation in homocysteine and methylenetetrahydrofolate reductase (MTHFR) gene variants, C677T and A1298C, have been linked with atherothrombosis. However their exact contribution to coronary artery disease (CAD) remains controversial. Moreover, data from Tunisian patients are scarse. We examined the association of MTHFR C677T and A1298C, and changes in plasma homocysteine in 352 Tunisian patients with angiographically-demonstrated CAD, and 390 age and gender-matched healthy subjects. Significantly higher frequency of 677T allele and homozygous 677T/T genotype were seen in patients vs. control subjects; the distribution of A1298C alleles and genotypes being comparable in the two groups. Specific MTHFR haplotypes comprising 677C/1298A (P < 0.001) and 677T/1298A (P < 0.001) were negatively and positively associated with CAD, respectively. Plasma homocysteine concentration was significantly higher in 677T/T genotype with respect to 677C/C and 677C/T genotypes in patients and controls, but homocysteine levels were generally comparable between both groups. Univariate analysis identified 677T/1298A (P = 0.033) haplotype to be positively associated with CAD, which remained significant by multivariate analysis after adjusting for a number of covariates (P = 0.038). MTHFR C677T, but not A1298C SNPs, is associated with CAD and with elevated homocysteine levels in a Tunisian population. The negative and positive association of the 1298A allele with CAD being indicative of a neutral (absent) effect of the A1298C SNP on disease pathogenesis.

OLR1,PON1andMTHFRGene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population

“…However, the T-A haplotype conferred an increased risk for coronary atherosclerosis severity, with a frequency of 40% in the high Gensini score group compared with 34.6% in the low Gensini score group. These results are in agreement with the finding by L. Ghazouani et al [27] where the C-A haplotype also indicated a protective role against CAD with an OR = 0.39 and 95% CI = 0.29-0.52. The T-A haplotype provided an increased risk for CAD with an OR = 2.35 and 95% CI = 1.62-3.38, which is also consistent with our findings.…”

“…The T-A haplotype provided an increased risk for CAD with an OR = 2.35 and 95% CI = 1.62-3.38, which is also consistent with our findings. In our study, however, the C-C and T-C haplotype frequency showed no difference between the two groups, whereas the Ghazouani et al [27] study indicated that they conferred an increased risk for CAD. Differences in ethnicity, dietary intake, exposure to environmental risk factors and sample size may be responsible for the discrepancies in the results.…”

C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population

“…24 Increased levels of inflammatory markers, such as the high-sensitivity C-reactive protein (hs-CRP), are predictive for increased risk of cardiovascular diseases and associated with atherosclerotic disease and insulin resistance. 25,26 Our study indicates that patients with MS-associated T2DM, the serum hs-CRP level and HOMA-IR are higher in those patients with MTHFR TT genotype than those with CC and CT genotypes.…”

Suppression of Homocysteine Levels by Vitamin B12 and Folates: Age and Gender Dependency in the Jackson Heart Study

“…6,7,8 A number of studies have explored the use of folic acid and vitamin B12 to decrease these levels, 9,10 but this relationship may not be as straightforward as once hoped. The recent ‘Vitamins to Prevent Stroke’ (VITATOPS) trial 11 examined the long-term daily effects of folic acid, vitamin B6, and vitamin B12 in reducing tHcy through conversion and excretion; 12 the regimen proved safe, but not significantly more effective than placebo in reducing major vascular events.…”