叶酸代谢相关基因与非综合征性唇腭裂的关系

Association of Genes Related to Folic Acid Metabolism with Non-syndromic Cleft Lip With or without Cleft Palate

目的:研究叶酸代谢相关基因在中国华北人群中与非综合征性唇腭裂的关系。方法:利用聚合酶链反应-限制性片段长度多态性方法,在115例非综合征性唇腭裂患者和192名正常对照个体中,对CBS和SHMT1基因2个单核苷酸多态性(SNP)rs397589和rs1979276进行检测。利用拟合优度卡方检验,分析基因型分布频率是否符合Hardy-Weinberg平衡定律;应用UNPHASED软件包分析单个基因多态性位点以及基因-基因相互作用与非综合征性唇腭裂的相关性。结果:2个基因上的SNP位点基因型频率分布均符合Hardy-Weinberg平衡;等位基因分布在NSCL/P组与对照组之间无显著性差异;rs397589TT和rs1979276TT基因型能增加NSCL/P患病风险(OR=2.60,95%CI=0.43-15.87;OR=1.62,95%CI=0.22-11.70);携带rs397589GT-rs1979276CT个体在患者中的频率高于对照组(χ2=4.780,P=0.029)。结论:CBS和SHMT1基因相互作用可能参与非综合征性唇腭裂的发生。

Objective：To investigate the association of two SNPs present at cystathionine-beta-synthase（CBS） and serine hydroxymethyltranferase 1（SHMT1） genes with non-syndromic cleft lip with or without cleft palate（NSCL/P） in northern China.Methods：Genotyping of rs397589 and rs1979276 presented at CBS and SHMT1 genes respectively was conducted by PCR-based restriction fragment length polymorphism（RFLP） in both patient and control group.The goodness-of-fit test was applied to test whether or not the genotypic distributions of two SNPs would be in Hardy-Weinberg equilibrium.The UNPHASED program was used to perform allelic and genotypic association and gene-gene interaction.Results：The genotypic distribution of two SNPs was not deviated from the Hardy-Weinberg equilibrium.No allelic association was found between individuds with NSCL/P and controls.Rs397589 TT and rs1979276 TT were more susceptible to NSCL/P（OR=2.60,95% CI=0.43-15.87,OR=1.62,95% CI=0.22-11.70）.The frequency of s397589 GT-rs1979276 CT combination in the patients was higher than that in healthy individuals.Conclusion：Interactional effect between CBS and SHMT1 gene may involve in occurrence of NSCL/P.