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

Abstract

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.

Hyperhomocysteinemia and folic acid metabolism in children living near the Chernobyl exclusion zone

“…The results obtained in the examination of adolescent children from the areas affected by the accident at the Chernobyl nuclear power plant are consistent with the results of a survey of adults from other countries in terms of correlations between H cy , vitamin B 9 and MTHFR:C677T polymorphism 8,9 .…”

Distribution and Determinants of Plasma Homocysteine Levels in a Preconception Population: A Retrospective Single-Center Study

“…In the present study, Hcy levels were higher in men than in women. A similar phenomenon has been reported in older adults and adolescents [ 24 – 27 ]. The present study not only confirmed that Hcy has a differential effect on different sexes during the preconception, but also showed that sex impacts the percentage of HHcy, similar to results of a recent Israeli study [ 28 ].…”

“…However, the cause of the sex-induced Hcy difference is still controversial. Physical activity, endogenous estrogens, rates of homocysteine remethylation, and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes are a few reasons [ 27 , 29 – 32 ].…”

Evaluation of acquired and hereditary risk factors for the development of thromboembolism in patients with systemic lupus erythematosus

“…However, it has been shown that the MTHFR C677T polymorphism increases the risk of at least one miscarriage in women with SLE [35]. In addition, MTHFR is known as the main regulatory enzyme in homocysteine metabolism, and some defects in this gene (especially C677T mutation) can lead to hyperhomocysteinemia [36]. It is known that there is a close relationship between high-plasma homocysteine levels and thromboembolism [15].…”