Systemic risk factors correlated with hyperhomocysteinemia for specific MTHFR C677T genotypes and sex in the Chinese population

Background: Methyltetrahydrofolate reductase (MTHFR) is a main regulatory enzyme in homocysteine (Hcy) metabolism. A common C677T mutation in the MTHFR gene results in decreased enzyme activity, which contributes to hyperhomocysteinemia (HHcy). Previous studies have shown that HHcy was correlated with various systemic diseases, such as cardiovascular disease, stroke, cancer, renal failure and so on. However, we hypothesized that HHcy in different genotype and sex groups may have different risk factors, which would lead to various pathologic states. Therefore, the aim of this study was to explore systemic information that are correlated with HHcy for specific MTHFR C677T genotypes and sex, which might be useful for predicting and preventing systemic diseases. Methods: This cross-sectional study was performed through November 2017 to July 2019. A total of 4,534 adults aged 20-75 y were selected for this study. All the participants underwent a physical examination, blood tests and MTHFRC677T genotyping. Multivariable linear regression was performed to explore the risk factors for HHcy for each sex and genotype. Results: The average of Hcy level is higher in the TT genotype than CC and CT genotypes (P=0.000). Multiple linear regression analysis identified the common protective factors (folate and Vit B12) and risk factor (Cr) for HHcy. Besides that, each group has its specific risk factors-female-CT (age, SBP, and Hb), female-TT (SBP and AST); male-CC (age, AST and Hb), male-CT (age and AST) and male-TT (SBP, AST, and Hb). Conclusions: HHcy was associated with different risk factors for each specific sex and genotype. These risk factors might be useful for predicting and preventing systemic diseases.