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