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The MTHFR C677T, APOE, and PON55 gene polymorphisms show relevant interactions with cardiovascular risk factors.

Coronary artery disease (CAD) often cannot be explained by conventional risk factors (1). Various polymorphisms, such as MTHFR C677T, which causes hyperhomocysteinemia in the TT form (2), PON M55L, which causes increased paraoxonase (PON) activity in the LL form (3), and APOE , in which the presence of the e4 allele adversely affects lipoprotein metabolism (4), have been associated with CAD. Most research to date has focused on the individual effects of each polymorphism on the specific metabolic pathways in which they are known to participate. Discrepancies as to the importance of the effects of these polymorphisms on cardiovascular risk factors exist (5)(6)(7). The aim of this study was to investigate the combined effect of the presence of two or more of these polymorphisms on their corresponding cardiovascular risk factors.

The study was performed in accordance with the guidelines of the institutions involved and was approved by the Hospital de Sant Joan and Jordi Gol Gorina Foundation ethics committees. All participants gave informed consent.

Fasting blood samples were obtained from 400 volunteers between 0800 and 0900, following an overnight fast. Blood was collected (10 mL in each tube) in two EDTA-containing Vacutainer Tubes for plasma and leukocyte preparation and in an untreated tube for serum preparation. The tubes were kept at 4 °C until processing (within 2 h). Serum and plasma were stored in aliquots of 250 μL to 1 mL in cryotubes at −80 °C until required for analysis, and leukocytes were prepared from the remaining pellet, from which DNA was extracted.

The genetic polymorphisms of the MTHFR , APOE , and PON 55 genes were analyzed according to previously described techniques (8)(9)(10)(11). Genotypes were identified independently by two observers, and the allele frequencies were calculated. The genotypes for …