中文摘要
先天性唇腭裂（CLP）是人类最常见的出生缺陷之一。本课题收集了206个核心家系（患者+双亲）以及174个正常对照组患儿，应用传递不平衡检验（TDT）和病例－对照方法，研究了IRF6、 MSX1和FGF3三个候选基因SNPs与非综合征型唇裂伴或不伴腭裂（NSCL/P）相关性。应用病例－对照设计，对环境暴露因素和IRF6、MSX1基因多态性与NSCL/P的关系进行单因素分析和多因素Logistic 回归分析, 研究哪些暴露因素是NSCL/P发生的显著性危险因素。在中国西部人群中，IRF6基因rs2235375、rs2235371（V274I）、rs642961、rs4844880四个SNP位点和MSXI基因CA重复序列多态性及 FGF3基因rs4980700、 rs4631909多态位点与NSCL/P的发病存在相关性，回汉族患者之间没有差异；MSX1基因的Q147I、rs3821949和rs12532 三个SNP位点与NSCL/P的发生无相关性；研究证实母亲孕早期患病史、母亲流产史、母亲孕早期服药史、父亲吸烟史与NSCL/P发病密切相关，母亲孕期维生素补充与NSCL/P的发病呈负相关。
英文摘要
Non-syndromic cleft lip with or without palate (NSCL/P) is a complex or multifactorial disease which has a high prevalence, 1.62/1000 live births, in China.We investigated the association between IRF6, MSX1 and FGF3 genes variants and NSCL/P, using both case-parent trio and case-control designs on samples from western China (in Ningxia population and western Chinese populations). Our study group consisted of 332 persons with NSCL/P, their parents, and 174 control individuals. On the basis of both genetic and environmental factors contribute to the NSCL/P, using the case-control study method, we further investigate the effects of the environmental exposure and IRF6, MSX1 gene polymorphisms to NSCL/P.Multifactor Logistic regression was used to analyses the results of investigation and detection. We found strong evidence of over- and under-transmission of the C allele (the Val allele) at rs2235371, and the C allele at rs2235375 in cleft case-parent trios (P = 0.013 and P = 0.000, respectively). There were significant differences in the frequency distributions of both genotypes and alleles when cases were compared with control infants at rs2235371 and rs2235375. Five specific haplotypes showed significant over- and under-transmission. The polymorphism of rs642961 and rs4844880 in IRF6 gene is associated with NSCL/
结题摘要
先天性唇腭裂（CLP）是人类最常见的出生缺陷之一。本课题收集了206个核心家系（患者+双亲）以及174个正常对照组患儿，应用传递不平衡检验（TDT）和病例－对照方法，研究了IRF6、 MSX1和FGF3三个候选基因SNPs与非综合征型唇裂伴或不伴腭裂（NSCL/P）相关性。应用病例－对照设计，对环境暴露因素和IRF6、MSX1基因多态性与NSCL/P的关系进行单因素分析和多因素Logistic 回归分析, 研究哪些暴露因素是NSCL/P发生的显著性危险因素。在中国西部人群中，IRF6基因rs2235375、rs2235371（V274I）、rs642961、rs4844880四个SNP位点和MSXI基因CA重复序列多态性及 FGF3基因rs4980700、 rs4631909多态位点与NSCL/P的发病存在相关性，回汉族患者之间没有差异；MSX1基因的Q147I、rs3821949和rs12532 三个SNP位点与NSCL/P的发生无相关性；研究证实母亲孕早期患病史、母亲流产史、母亲孕早期服药史、父亲吸烟史与NSCL/P发病密切相关，母亲孕期维生素补充与NSCL/P的发病呈负相关。