Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians

Prithiksha Ramkaran; Alisa Phulukdaree; Sajidah Khan; Devapregasan Moodley; Anil A Chuturgoon

doi:10.1016/j.gene.2015.06.044

Methylenetetrahydrofolate reductase C677T polymorphism is associated with increased risk of coronary artery disease in young South African Indians

Gene. 2015 Oct 15;571(1):28-32. doi: 10.1016/j.gene.2015.06.044. Epub 2015 Jun 18.

Authors

Prithiksha Ramkaran¹, Alisa Phulukdaree², Sajidah Khan³, Devapregasan Moodley¹, Anil A Chuturgoon⁴

Affiliations

¹ Discipline of Medical Biochemistry and Chemical Pathology, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa.
² Department of Physiology, School of Medicine, Faculty of Health Sciences, Prinshof Campus, University of Pretoria, South Africa.
³ Department of Cardiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
⁴ Discipline of Medical Biochemistry and Chemical Pathology, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa. Electronic address: CHUTUR@ukzn.ac.za.

PMID: 26095803
DOI: 10.1016/j.gene.2015.06.044

Abstract

Methylenetetrahydrofolate reductase (MTHFR) reduces 5',10'-methylenetetrahydrofolate to 5'-methyltetrahydrofolate, and is involved in remethylation of homocysteine to methionine, two important reactions involved in folate metabolism and methylation pathways. The common MTHFR C677T single nucleotide polymorphism (SNP) (rs1801133) has been associated with raised levels of homocysteine, a well known risk factor for coronary artery disease (CAD). CAD is a major cause of mortality worldwide. The age of onset of this chronic disorder is on the decline, particularly in the Indian population. Indians in South Africa (SA) have a higher prevalence of premature CAD compared to Black South Africans. The MTHFR C677T SNP has not been investigated in the SA Indian population. The present study therefore investigated the MTHFR C677T SNP in young SA Indian males with CAD compared to young Indian and Black male controls. A total of 290 subjects were recruited into this study which included 106 CAD patients (diagnosed on angiography, mean age 37.5, range 24-45 years), 100 Indian male controls (mean age 37.5, range 28-45 years), and 84 Black male controls (mean age 36.4, range 25-45). Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) was used to genotype CAD patients and healthy controls. Data for clinical markers were obtained from pathology reports. There was a significant association between the 677 MTHFR variant (T) allele and CAD patients compared to the healthy Indian controls (p=0.0353, OR=2.105 95% CI 1.077-4.114). Indian controls presented with a higher frequency of the variant allele compared to Black controls (7% vs. 2% respectively, p=0.0515 OR=3.086 95% CI 0.9958-9.564). The MTHFR C677T SNP did not influence levels of total cholesterol, LDL, HDL, triglycerides, fasting glucose, fasting insulin, HbA1c or hsCRP. The higher frequency of the MTHFR 677 variant allele in South African Indians may be a contributing factor to the higher risk profile for the development of premature CAD in Indians.

Keywords: Homocysteine; MTHFR C677T; Methylenetetrahydrofolate reductase; Premature coronary artery disease; Single-nucleotide polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Black People / genetics
Coronary Artery Disease / ethnology
Coronary Artery Disease / genetics*
Gene Frequency
Genetic Predisposition to Disease / ethnology
Genetic Predisposition to Disease / genetics*
Genotype
Humans
Indians, South American / genetics*
Linkage Disequilibrium
Male
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Middle Aged
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide*
Risk Factors
South Africa
Young Adult

Substances

MTHFR protein, human
Methylenetetrahydrofolate Reductase (NADPH2)