Abstract:

Abstract：Objective To assess the association between polymorphism of Methylenetetrahydrofolate reductase （MTHFR） gene A1298C locus and nonsyndromic cleft lip with or without cleft palate（NSCL/P） in Shanxi province. Methods From September 2010 to April 2012，150 patients and their parents（containing 135 NSCL/P nuclear family） and 150 controls from Shanxi province were collected . The polymorphism of MTHFR gene A1298C locus was analyzed by the methods of polymerase chain reaction and restriction fragment length polymorphism technique（PCR-RFLP）. Case-control analysis，transmission-disequilibrium test（TDT）and haplotype-based haplotype relative risk analysis（HHRR）were used to study the correlation between the gene mutation and NSCL/P. Results The Hardy-Weinberg equilibrium results showed that，genotypes of case group and control group both did not deviate from Hardy-Weinberg equilibrium（P > 0.05）. By case-control analysis，the significant difference was found in the frequencies of AA，AC and CC genotypes of MTHFR A1298C locus between the offsprings from case group and control group（P < 0.05）. These significant differences were found in the frequencies of A allele and C mutant allele of MTHFR A1298C locus in the offsprings from case group and control group （P < 0.05），respectively. TDT analysis suggested a linkage in the presence of disequilibrium（P < 0.05）and results of HHRR analysis（P < 0.05），both indicating an association between MTHFR A1298C locus variant and the risk of NSCL/P. Conclusion The single nucleotide polymorphism of MTHFR A1298C locus is associated with the development of NSCL/P in Shanxi province.

Key words: MTHFR, NSCL/P, nuclear families, genetic polymorphism

摘要：

目的 探讨亚甲基四氢叶酸还原酶（MTHFR）基因A1298C多态性与山西人群非综合征性唇腭裂（nonsyndromic cleft lip with or without cleft palate，NSCL/P）的相关性。方法 选取2010年9月至2012年4月山西地区150例NSCL/P患者及其父母作为病例组（其中有135个完整的NSCL/P核心家系），150例正常新生儿作为对照组，应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）分析方法，对MTHFR基因A1298C位点的多态性进行检测，利用人群关联研究分析、病例组核心家系的传递不平衡检验（TDT）、单体型的相对危险度（HHRR）分析来研究该突变与NSCL/P的相关性。结果 病例组和对照组人群基因型均未偏离Hardy-Weinberg遗传平衡定律（P > 0.05）；病例组与对照组进行子代间比较，AA、AC、CC 3种基因型分布差异有统计学意义（P < 0.05），A等位基因和C突变等位基因的分布差异均有统计学意义（P < 0.05）；NSCL/P核心家系TDT检验，差异有统计学意义（P < 0.05），表明突变等位基因C存在着传递失衡的现象；HHRR检验结果表明，MTHFR基因A1298C位点多态性由双亲传递给患病子女的等位基因（C/A）频率差异有统计学意义（P < 0.05）。结论 MTHFR基因A1298C位点多态性与山西人群NSCL/P的发生存在关联。

关键词: 亚甲基四氢叶酸还原酶, 非综合征性唇腭裂, 核心家系, 基因多态性