RESUMO
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-beta-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 micro mol/l, respectively which are higher than the upper normal limit of this biomarker [15micro mol/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
RESUMO
To find out the prevalence of hyperhomocysteinemia, and deficiencies of folate, vitamin B6 and vitamin B12 in an urban population in Karachi, Pakistan. In a pre and post experimental study, eight hundred and seventy-two apparently healthy adults [aged 18-60 years; 355 males and 517 females] were recruited from a low-income urban locality in East of Karachi from February 2006 to March 2007. Fasting venous blood was obtained. Serum was analyzed for folate and vitamin B12. Plasma was analyzed for pyridoxal phosphate [PLP, coenzymic form of B6] and total homocysteine. A group of vitamin-deficient individuals [n=194] was given 3-week supplementation with folic acid [5mg/day], methycobalamin [0.5mg/day] and pyridoxine hydrochloride [vitamin B6, 50 mg/day]. After supplementation, serum/plasma levels of folate, vitamin B12, PLP and homocysteine were again determined. Prevalence of hyperhomocysteinemia [>15micromol/l] was 32%. Similarly percent values of folate deficiency [<3.5ng/ml], vitamin B6 deficiency [PLP<20 nmol/l] and vitamin B12 deficiency [<200pg/ml] in the study population were 27.5%, 33.7% and 9.74%, respectively. Hyperhomocysteinemia was associated with male sex, folate deficiency, vitamin B12 deficiency [OR [95%CI], 8.3[5.7-12.1]; 2.5[1.76-3.58]; 2.6[1.5-4.5], respectively]. A 3-week supplementation with folic acid, methycobalamin and pyridoxine hydrochloride in vitamin-deficient subjects decreased plasma homocysteine levels by 37%. High prevalence estimates of folate, vitamin B12, and vitamin B6 deficiencies appear to be the major determinants of hyperhomocysteinemia in a low income general population in Karachi