Single Nucleotide Polymorphisms in Key One-Carbon Metabolism Genes and Their Association with Blood Folate and Homocysteine Levels in a Chinese Population in Yunnan

Objective: One-carbon metabolism (OCM) is essential for DNA synthesis and methylation. Single nucleotide polymorphisms (SNPs) within OCM genes may affect folic acid (FA) metabolism, disrupt homocysteine (Hcy) homeostasis, and increase the risk of disease. This study investigated the relationship between SNPs in key OCM genes and their association with blood FA and Hcy levels in a healthy population in Yunnan, China. Methods: Six SNPs within five key OCM genes (MTHFR C677T, MTHFR A1298C, MS A2756G, MTRR A66G, CBS T833C, and SHMT C1420T) were genotyped in 300 healthy volunteers (148 males and 152 females) using polymerase chain reaction/restriction fragment length polymorphism. Blood folate [serum FA (SFA) and red blood cell folate (RBC FA)] and Hcy levels were determined by chemiluminescence immunoassays and enzymatic assays. Results: Subjects with the MTHFR 677TT genotype had significantly higher Hcy levels and RBC FA concentrations compared with those harboring the MTHFR 677CC/CT genotypes (p<0.01). Both Hcy and blood FA concentrations were also increased in subjects with MS 2756AA, as well as those within CBS 833TT, when compared with those with MS 2756AG/GG (p<0.05) and CBS 833TC/CC (p<0.05) genotypes, respectively. Subjects harboring the combined genotype of MTHFR 677TT and MS 2756AA had a higher Hcy concentration than those carrying other MTHFR and MS combinations (p=0.002). Similarly, subjects harboring the combination of CBS 833TT with MTHFR 677TT had higher Hcy concentrations than those harboring other CBS and MTHFR combinations (p=0.011). Conclusions: The genotypes involving the MTHFR C677T, MS A2756G, and CBS T833C polymorphisms, including combinations of these genotypes, were the most important factors associated with blood FA and Hcy levels of the investigated SNPs in the OCM genes.