Lack of association of methylenetetrahydrofolate reductase 677C>T mutation with coronary artery disease in a Pakistani population

Abstract

Pakistanis belong to the South Asian population which has the highest known rate of coronary artery disease. Folic acid deficiency also appears to be highly prevalent in this population. Methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism decreases the activity of this enzyme and can be associated with mild to moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with coronary artery disease. To assess the value of genotyping the MTHFR 677C>T dimorphism, we carried out a case-control study of dimorphism 677C>T for putative association with myocardial infarction (MI) among Pakistani nationals. We investigated a sample population of 622 Pakistanis consisting of 225 controls and 397 patients with clinical diagnosis of acute MI (AMI). MTHFR C677T alleles were determined by assays based on polymerase chain reaction and restriction endonuclease analysis. Frequencies of C alleles were 0.87 among controls and 0.86 among AMI patients. The MTHFR 677C>T dimorphism showed no association with MI (χ2 = 0.25, 1df, P=0.62), serum levels of folate and vitamin B12 and plasma level of vitamin B6. A significant association, however, was found between homozygous 677T genotype and plasma levels of homocysteine. Multivariate analysis of the data showed that in case of log homocysteine, age and MTHFR genotypes were significantly different (P<0.001). In case of B12, smoking and age were found to be statistically significant (P<0.001), while in case of serum folate only smoking was found to be significant (P<0.001). The results indicate that MTHFR 677C>T polymorphism, though associated with homocysteine levels, confers no significant risk of coronary artery disease in the Pakistani population investigated here. We suggest that the higher incidence of AMI in South Asia occurs through mechanisms other than the MTHFR related pathways.

Genetic Polymorphisms and the Risk of Myocardial Infarction in Patients Under 45 Years of Age

“…In this population the frequency of the TT genotype was more common among patients with coronary artery disease than the control group (Li 2012). Regardless of the results of recent meta-analyses, the role of the C677T polymorphism in the etiopathology of coronary artery disease and myocardial infarction is still controversial, and it has not been observed in some populations (Balogh et al 2012; Iqbal et al 2005). This discrepancy may be related to differences in genetic background in the populations studied or to differences in the selection of patients and healthy controls.…”

Polymorphisms of methylenetetrahydrofolate reductase gene as the genetic predispositions of coronary artery diseases in eastern India

“…[ 24 ] A study investigated that MTHFR 677CT polymorphism, though associated with homocysteine levels, confers no significant risk of CAD in the Pakistani population. [ 25 ] Limited data are available for other Asian populations, especially Indians. [ 26 – 28 ] Nair et al ,[ 26 ] reported that heterozygosity for thermolabile MTHFR mutation was associated with hyperhomocysteinemia, which could be a risk factor for CAD in the Indian population.…”

Prevalence of the C677T Single-Nucleotide Polymorphism in the Methylenetetrahydrofolate Reductase Gene Among Pakistani Ethnic Groups

“…Some groups have been shown to be genetically distinct (Qamar et al, 2002;Mansoor et al, 2004). Data regarding C677T occurrence in Pakistan are almost nonexistent except a few reports describing association of this mutation with primary closedangle glaucoma (Michael et al, 2008) and coronary artery disease (Iqbal et al, 2005). Due to high geographic and social diversity existing in Pakistan (Ahmed and Sirageldin, 1993), we hypothesized a varied prevalence of C677T mutation.…”