HNF-6基因单体型与胆道闭锁发病的相关性

目的 探讨HNF-6基因单核甘酸多态性(single nueleotide polymorphisms,SNPs)与胆道闭锁(biliary atresia,BA)发病的相关性.方法 2005年至2008年之间收治的经临床诊断、术中胆道造影检查证实均为Ⅲ型BA的息儿作为病例组,117例,男72例,女45例,年龄(2.94±2.43)个月.对照组为125名没有遗传疾病或出生缺陷的年龄段及男女比例与病例组基本匹配的正常婴幼儿.对两组婴幼儿外周血进行基因组DNA提取,用Taqman SNP genotyping assay分型技术对SNPs位点-400G/T(rs2456523)、1666C/T(rs2456525)和858G/T(rs2075613)进行分型和所组成的单体型分析,用χ2检验统计分析病例组和对照组等位基因频率、等位基因型频率及患病风险;同时用Haplovieaw软件对HNF-6单体型组成、单体型频率及其患病风险进行统计分析;对一部分结果进行测序验证.结果 BA组与对照组HNF-6 SNPs:rs2456525 C和T等位基因频率C(67.1% vs.59.6%)、T(32.9% vs.40.4%),差异无统计学意义(P>0.05);CC(41.1% vs.33.6%)、CT(52.1% vs.52.0%)和TT(6.8% vs.14.4%)等位基因型频率差异无统计学意义(P>0.05).rs2456523 G和T等位基因频率G(34.2% vs.40.8%)、T(65.8% vs.59.2%),差异无统计学意义(P>0.05);TT(39.3% vs.35.2%)、GT(53.0% vs.48.0%)和GG(7.7% vs.16.8%)等位基因型频率差异无统计学意义(P>0.05).rs2075613 G和T等位基因频率G(86.8% vs.84.8%)、T(13.2% vs.15.2%)差异无统计学意义(P>0.05);GG(74.4% vs.71.2%)、GT(24.8% vs.27.2%)和TT(0.9% vs.1.6%)等位基因型频率差异无统计学意义(P>0.05);而胆道闭锁组与对照组HNF-6常见单体型CTG频率差异有统计学意义(P=0.028),单体型CTG的患病风险为1.511.结论 HNF-6 rs2456525、rs2456523和rs2075613各自多态位点与BA无关;HNF-6基因常见单体型CTG与中国人群中BA发生相关联,具有CTG单体型人患BA的危险性相对较高.

Association of hepatocyte nuclear factor 6 haplotype with biliary aresia

Objective To investigate the association of single nucleotide polymorphisms(SNPs) of hepatocyte nuclear factor 6 (HNF6) gene and their haplotypes in patients with biliary atresia (BA).Methods DNA was isolated from 117 BA patients and 125 healthy controls.The SNPs of HNF 6 were genotyped using Taqman SNP genotyping assay for 1666C/T (rs2456525)、-400G/T (rs2456523)、858G/T(rs2075613) allelic discrimination.The allele and genotype frequencies and risk factors of BA subjects and controls were analyzed by Chi-square test.The haplotype were reconstructed and the common haplotypes frequencies were evaluated by Haploview software.Results No significant differences were found in genotyping frequencies of CC (41.1% vs.33.6%),CI (52.1% vs.52.0%) and TT (6.8% vs.14.4%) as well as alleles C (67.1% vs.59.6%) and T(32.9% vs.40.4%) in rs2456525,frequencies of GG (7.7% vs.16.8%),GT (53.0% vs.48.0%) and TT (39.3% vs.35.2%) as well as alleles G (34.2% vs.40.8%) and T (65.8% vs.59.2%) in rs2456523 and frequencies of GG (74.4% vs.71.2%),GT (24.8% vs.27.2%) and TT (0.9% vs.1.6%) as well as alleles G (86.8% vs.84.8%) and TT (13.2% vs.15.2%) in rs2075613 between BA subjects and controls.But the frequencies in the CTG hapolatype reconstructed by the 3 SNPs were found to be associated with BA (P=0.028).The disease risk of the CTG hapolatype was 1.511.Conclusions The allelic variation rs2456525,rs2456523 and rs2075613 in HNF-6 gene might not individually contribute to the susceptibility of BA subjects.Yet the CTG hapolatype may be related to BA.Individuals having CTG hapolatype are at a relatively high risk for BA.