Polymorphism (C677T) of 5,10 Tetrahydromethylenefolate-Reductase (THMFR) among Brazilian Normolipemic Young Adults with Coronary Artery Disease

 
M. Zangrando, J.S. Hotta, J.A. Marin-Neto, M.A. Zago, J.E. Dos Santos.
Department of Medicine, Faculty of Medicine of Ribeirão Preto, USP, Ribeirão Preeto, Brazil.
 

Several epidemiological studies have identified hyperhomocysteinemia (Hcy) as an independent risk factor for coronary artery disease (CAD). Structural abnormalities of THMFR, an enzyme that catalyzes the remethylation of homocysteine, may cause Hcy. A polymorphic variants of THMFR (C667T) which determines the exchange of one alanine (A) residue with a valine (V) residue in the structure of THMFR has been recently described. Some studies suggest that the VV genotype and not the AV or AA genotype is associated with Hcy and CAD. To determine the prevalence of the VV genotype in a group of normolipemic young patients with CAD and the frequency of the V gene in a Brazilian population. The study was conducted on 97 individuals with an angiographic diagnosis of CAD, who were compared to 73 individuals without ischemia or coronary artery damage (control group) as determined by angiography. Cholesterolemia was 189.7 + 34.1 mg% in the CAD group (mean age: 43.5 + 6.9 years) and 171.2 + 35.4 mg% in the control group (mean age: 44.5 + 7.1 years). The PCR method of Morita et al. was used to amplify the desired segments. The final amplification product was submitted to digestion with the restriction enzyme HinfI and polymorphism was visualized by 6% polyacrylamide gel electrophoresis with ethidium bromide under UV light, followed by photographic documentation. Twenty individuals (20.6%) with the VV genotype were detected in the CAD group and 6 (8.2%) in the control group (p<0.026), with an odds ratio of 2.86 (95% confidence interval: 1.10-7.65). Sixty-three individuals with the VV and AV genotypes were detected in the CAD group (37%) and 33 in the control group (20%) (p<0.018) with an odds ratio of 2.19 (95% confidence interval of 1.174 to 4.086). The frequency of the V gene in the population is 0.36 (CAD = 0.43, and control group = 0.27, p<0.003). The presence of the V gene is a risk factor for CAD in normolipemic young adults. The frequency of the V gene is comparable to that in the French Canadian (0.38) and Japanese (0.42) populations.

Research supported by FAPESP and CNPq.

 
 
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