Asociación de variantes funcionales en genes del metabolismo de la homocisteína con riesgo de trombosis venosa profunda e hiperhomocisteinemia en individuos del Sur de Chile

Abstract

Background: Deep Venous Thrombosis (DVT) is an important health problem in modern society. Recent evidence suggests an association between functional variants in homocysteine metabolism genes and DVT. However, findings in different populations have been contradictory. In this work, we evaluated the potential association between the presence of polymorphisms in homocysteine metabolism genes, DVT susceptibility and hyperhomocysteinemia in Chilean subjects. Methods: A total of 231 individuals, 77 patients with diagnosis of DVT and 154 controls were inclu- ded in this study. Common variants in Metylenete- trahydrofolate reductase (MTHFR) and Cistationine β-synthetase (CBS) genes were genotyped by PCR- RFLP. Basal homocysteine was quantified by Fluores- cence Polarization Immunoassay. Results: Genotype distribution and allelic frequen- cies of MTHFR C677T polymorphism were signifi- cantly different between patients and controls. Odds Ratio for DVT associated to homozygous status was 3.68 (95%C.I., 1.628–8.337, p<0.01). On the other hand, the genotype distribution of the CBS 844ins68 variant was similar in both groups (OR 1.82, 95%C.I.: 0.636-5.234, p=0.257). In addition, the individuals ca- rrying the MTHFR 677TT homozygous genotype ex- hibited higher levels of homocysteine. Conclusion: The MTHFR C677T polymorphism constituted a molecular biomarker of DVT in Chilean population, and related to higher levels of homocys- teine in homozygote subjects. The results suggest that the molecular detection of this polymorphism should be included in the basic screening for thrombophilia in our population.