Role of Methylenetetrahydrofolate Reductase Gene Polymorphisms (C677T, A1298C, and G1793A) in the Development of Early Onset Vasculogenic Erectile Dysfunction

Abstract

The methylenetetrahydrofolate reductase (MTHFR) gene plays a key role in the metabolism of folate and homocysteine (Hcy) and its mutations have been associated with high serum Hcy level. Elevated serum Hcy has been linked to impaired endothelial function and occlusive vascular disease. We studied the association among the different genotypes of all three MTHFR polymorphisms (C677T, A1298C, and G1793A) and the risk of early-onset vasculogenic erectile dysfunction (VED). We performed a case-control study of 114 men with early-onset VED and 228 age-matched controls. Genotyping of MTHFR gene polymorphisms was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. We also measured plasma lipids, Hcy, folate, and vitamin B12 levels. Patients with early-onset VED had higher serum Hcy levels (12.29 ± 2.32 vs. 9.82 ± 2.35 μmol/L, p = 0.001) and higher prevalence of 677TT homozygocity compared to controls (15.8% vs. 11.4%, p = 0.01). Serum Hcy concentration was significantly higher in individuals with 677TT, 1298CC, and 1793GG genotypes. Subgroup analysis according to severity of ED (mild, moderate, and severe) showed that patients with severe VED had higher serum Hcy levels compared to patients with mild VED (13.48 ± 2.51 vs. 11.21 ± 2.32 μmol/L, p = 0.001). Odds ratio seems to demonstrate that individuals with the MTHFR 677TT genotype and the 677TT + 1298AC combined genotype had a 3.16- and 3.89-fold increased risk for developing VED, suggesting a possible association of MTHFR polymorphisms with the risk of early-onset VED.