title: Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population.
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.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Mohammad Perwaiz
authors.initials: MP
authors.lastname: Iqbal
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Khalida
authors.initials: K
authors.lastname: Iqbal
authors.affiliation: National Institute of Cardiovascular Diseases, Karachi, Pakistan.
authors.forename: Asal Khan
authors.initials: AK
authors.lastname: Tareen
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Siddiqa
authors.initials: S
authors.lastname: Parveen
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Naseema
authors.initials: N
authors.lastname: Mehboobali
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Haider
authors.affiliation: Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Saleem Perwaiz
authors.initials: SP
authors.lastname: Iqbal
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009203:Myocardial Infarction / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D010154:Pakistan; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase