中文摘要：

目的：探索中国人群中叶酸／同型半胱氨酸代谢通路上的基因多态性与非综合征型唇腭裂（isolated non-syndromic cleft lip with or without eleft palate，NSCL／P）的关联关系及可能存在的基因一环境交互作用。方法：在806个中国人群的核心家庭中，对叶酸／同型半胱氨酸通路上的18个基因进行了传递不平衡检验以及基因一环境交互作用分析。环境因素包括母亲孕期吸烟、被动吸炯、饮酒及服用多维生素补充剂。结果：经过质量控制的筛选，共对257个位点的单核苷酸多态性（single nucleotide polymorphisms，SNPs）进行了传递不平衡检验及交互作用分析，结果显示，共有4个SNPs（rs6428977、rsl2060264、rs7730643和rs4920037）与NSCL／P显著关联（P〈0．05）。但在Bon—ferroni校正后，该通路上的代谢基因位点与NSCL／P之间的关联不具有统计学意义。经多重检验校正后，未发现常见孕期环境暴露与叶酸／同型半胱氨酸代谢通路上的基因多态性存在显著的交互作用。结论：未发现叶酸／同型半胱氨酸代谢通路上的基因多态性与NSCL／P之间存在关联。

英文摘要：

Objective ：To explore the association between 18 candidate genes encoding enzymes on the folate/homocysteine metabolism pathway and non-syndromie cleft lip with or without cleft palate （ NSCL/ P） in Chinese populations. Methods： A total of 806 NSCL/P trios were drawn by an international consortium, which conducted a genome-wide association study using a case-parent trio design to investigate genes affecting risks to NSCL/P. The transmission disequilibrium test （TDT） was used for deviation from Mendelian expectations for 257 SNPs in 18 folate/homocysteine metabolism-related genes. The interactions between markers in these gene and environmental risk factors were also tested using conditional Logistic regressions. Results ： Although four SNPs （ rs6428977, rs12060264, rs7730643 and rs4920037 ） showed nominal significant association with NSCL/P in the TDT on 806 NSCL/P trios （P 〈0.05） , no significant evidence of linkage and association remained in all the SNPs after Bonferroni correction. Similar tests for interactions between genes and maternal smoking, environmental tobacco smoke, alcohol consumption and multi-vitamin supplementation during pregnancy did not attain statistical significance after correction for multiple comparisons. Conclusion： Folate/homocysteine metabolism-related genes could not influence the risk of NSCIJP.