Correlation analysis of MTHFD1 gene polymorphisms and neural tube defects in Han population of Northern China

Background Neural tube defects (NTDs) is a common birth defects worldwide. The methylenetetrahydrofolate dehydrogenase1 (MTHFD1) gene has been proved to play an important role in folate metabolism, which was strongly associated with the increased NTDs risk. The study is aimed to explore the correlation of single nucleotide polymorphisms (SNPs) in MTHFD1 gene with NTDs susceptibility. Methods A case-control study was conducted on children who included 152 NTDs patients and 169 healthy controls. Tag-SNPs were identified in HapMap database. Then, we investigated the association between NTDs and four selected tag-SNPs in MTHFD1 gene: rs1950902, rs2236225, rs2236224, rs11849530. We also performed a meta-analysis based on previous published studies to further evaluate the association. Results The results indicated that rs2236225 polymorphism displayed a significant association with NTDs risk (AA vs. GG: OR = 2.862, 95%CI = 1.022ཞ8.015; GA + AA vs. GG: OR = 1.619, 95%CI = 1.040ཞ2.520; A vs. G: OR = 1.500, 95%CI = 1.061ཞ2.120). In addition, rs2236224 polymorphism was correlated with increased NTDs risk (TT vs. CC: OR = 2.559, 95%CI = 1.128ཞ5.804; CT + TT vs. CC; OR = 1.631, 95%CI = 1.041ཞ2.556; T vs C: OR = 1.489, 95%CI = 1.072ཞ2.068). Further analysis showed the harmful effect of rs2236225 polymorphism was further supported by the result of meta-analysis. Meanwhile, haplotype analysis results showed that A-A and T-A haplotypes were correlated with increased NTDs risk, but C-A haplotype might decrease NTDs risk. Conclusions The results indicated that rs2236225 and rs2236224 polymorphisms of MTHFD1 gene were significantly associated with NTDs susceptibility in Han population of Northern China.

A genetic variant in the gene encoding fibrinogen beta chain predicted development of hypertension in Chinese men

SummaryFibrinogen, a major determinant of blood viscosity, is an acute phase protein associated with cardiovascular disease. We studied the association of hypertension with single nucleotide polymorphisms (SNPs) in the gene encoding the fibrinogen β chain (FGB). Three tagging SNPs (rs1025154, rs4220 and rs1044291) were selected from the HapMap database on Han Chinese. Genotypes were determined in 1,294 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. There were 199 hypertensive subjects at baseline. Among 1,095 subjects normotensive at baseline, 178 developed hyper-tension during a median follow-up period of 6.4 years. Among the three tagging SNPs, rs4220 showed significant association with hypertension at both baseline (odds ratio [OR]=1.49, p=0.004) and at follow-up (OR=1.32, p=0.013). The minor A allele of this SNP was associated with higher plasma fibrinogen level (β=0.144, p<0.001 at baseline and β=0.130, p<0.001 at follow-up). Among subjects normotensive at baseline, this SNP was also associated with the development of hyper-tension in men (OR=1.52, p=0.022), but not in women. The SNP rs4220 in FGB, which leads to the substitution of arginine by lysine at position 448, is independently associated with plasma fibrinogen level and hypertension in Hong Kong Chinese. This suggests a possible causal role of fibrinogen in hypertension development, especially in men.