Association between the BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy in patients with hyperhomocysteinemia.

Oral folate is currently the most common treatment for hyperhomocysteinemia (HHcy), which seriously threatens human health, but its efficacy is unsatisfactory. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme that regulates Hcy metabolism. We investigated the association between the BHMT rs3733890 and the efficacy of oral folate therapy for HHcy in the Chinese Han population and analysed the effects of gene-environmental interactions on the efficacy. Blood samples were collected from 1071 eligible patients at baseline, and these individuals received subsequent folate treatment for 90 days. A total of 638 patients included in the final analysis were grouped into the treatment success group or the treatment failure group based on posttreatment Hcy levels. Hcy concentrations were measured by fluorescence polarization immunoassay. Time-of-flight mass spectrometry (MassArray system) was used to assess the genotype of BHMT rs3733890. Stratified analyses based on additive models and generalized multifactor dimensionality reduction were used to explore gene-environmental interactions. The genotype distribution presented distinct differences in the two groups. The mutant genotype and allele had significantly increased risk of treatment failure (p < 0.05). Furthermore, synergistic effects of the BHMT rs3733890 polymorphism with environmental risk factors (smoking, drinking, past history) on the efficacy of therapy were also found. However, future, large well-designed studies, as well as mechanistic studies, are still needed to validate our findings.