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Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population
Mohammad Perwaiz Iqbal1, Khalida Iqbal1, Asal Khan Tareen2
1Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Insights
Genetic factors for premature heart disease in Pakistan were investigated. Common gene variations in the homocysteine pathway, including methylenetetrahydrofolate reductase (MTHFR), were not associated with premature acute myocardial infarction (AMI) in this population.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Biochemistry
Background:
- Premature coronary heart disease is highly prevalent in Pakistan, suggesting a genetic predisposition.
- Previous studies have not investigated the role of homocysteine pathway gene polymorphisms in Pakistani populations regarding premature heart disease.
Purpose of the Study:
- To investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; and cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in Pakistani patients.
- To analyze plasma homocysteine, folate, and vitamin B12 levels in relation to these polymorphisms and premature AMI.
Main Methods:
- A cross-sectional study involving 143 premature AMI patients (age <45 years) and 153 healthy controls.
- DNA genotyping using PCR-RFLP for MTHFR, MS, and CBS polymorphisms.
- Biochemical analysis of plasma/serum homocysteine, folate, and vitamin B12 levels.
- Statistical analysis using one-way ANOVA and chi-squared test.
Main Results:
- Mean plasma homocysteine levels in both premature AMI patients (23±17.2 μmol/l) and healthy controls (23±13.4 μmol/l) exceeded the normal upper limit (15 μmol/l).
- MTHFR 677 CT genotype in controls and MTHFR 677 TT genotype in AMI patients showed significantly increased plasma homocysteine (p<0.05).
- No significant association was found between the studied MTHFR, MS, and CBS polymorphisms and premature AMI in the Pakistani population.
Conclusions:
- Common polymorphisms in MTHFR, MS, and CBS genes do not appear to play a significant role in the development of premature AMI among Pakistanis.
- Elevated homocysteine levels are present in this population, but the common genetic variants studied do not explain the predisposition to premature heart disease.
Abstract:
High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-β-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age <45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 μmol/l, respectively which are higher than the upper normal limit of this biomarker (15μmol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value <0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population.