Role of homocysteine & MTHFR C677T gene polymorphism as risk factors for coronary artery disease in young Indians.
OBJECTIVE
Hyperhomocysteinaemia (HCA) either due to mutation of MTHFR gene or deficiency of vitamin B 12 and folic acid, has been reported as a risk factor for coronary artery disease (CAD). The present study was aimed to determine plasma homocysteine (Hcy) levels and to evaluate MTHFR C677T gene polymorphism as risk factors for CAD, and to study the role of Hcy in conjunction with a few other risk factors of CAD in young Indians. The effect of vitamin B12 and folic acid supplements on the raised plasma Hcy levels in patients of CAD was also assessed.


METHODS
The present study included 199 consecutive angiography confirmed CAD patients, <45 yr of age, without any other known pro- coagulant state and 200 age- and sex-matched healthy controls. Fasting blood samples were collected in EDTA and plasma Hcy was estimated by ELISA test and the MTHFR C677T polymorphism detection was carried out by PCR-RFLP method.


RESULTS
Significant difference (P<0.001) was found between mean fasting levels of plasma Hcy in cases (22.14 ± 10.62 μmol/l) and controls (17.38 ± 8.46 μmol/l) with an Odds ratio as 1.93 (95% CI, 1.27-2.94). Levels of cholesterol, LDL, and triglycerides were significantly (P<0.001) higher in cases compared with controls.


CONCLUSIONS
Our study showed significant correlation between hyperhomocysteinaemia and coronary artery disease. Multivariate analysis by logistic regression of the various risk factors of CAD, found high levels of Hcy, cholesterol, LDL and low levels of HDL and smoking as independent predictors of CAD when all other factors were controlled. Significant post-treatment decrease found in HCA was easily modifiable by vitamin intervention irrespective to their CT or TT genotype of C677T MTHFR gene. Further studies to look at the plasma levels of folate and cobalamines and their association with Hcy are required to be done.
Department of Pathology, Armed Forces Medical College (AFMC), Pune, India. maj_sgupta@yahoo.co.in
Santosh Kumar
SK
Gupta
Jyoti
J
Kotwal
Atul
A
Kotwal
Anil
A
Dhall
Salil
S
Garg
D000328:Adult; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D056726:Genetic Association Studies; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics* / Q000378:metabolism; D007194:India; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D014280:Triglycerides / Q000097:blood; D014805:Vitamin B 12 / Q000008:administration & dosage
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12