端粒酶逆转录酶基因多态性与非综合征型唇腭裂的相关性研究

Assocation between the TERT Gene Polymorphisms and NSCL/P

目的采用病例—对照研究,探讨端粒酶逆转录酶(TERT)基因单核苷酸多态性与宁夏人群非综合征型唇裂伴或不伴腭裂(NSCL/P)之间的相关性。方法收集唇腭裂患者共计504人,同期产科的正常新生儿455名为对照组,收集病例组个体外周静脉全血5 mL。留取对照组新生儿个体脐带血5 mL。选取TERT基因11个tagSNP位点,利用AgriSeqTM靶向测序技术进行基因分型,对符合哈温平衡的SNPs位点进行连锁分析和单倍型分析,探讨上述位点是否与NSCLP存在相关性。结果对照组样本rs33954691、rs11133715、rs2736115、rs4246742、rs56345976、rs33963617、rs10069690、rs4975538、rs2736100、rs2853677、rs273610911个SNPs位点符合率平衡。其中rs33963617SNP位点的等位基因率数和基因型频数在病例组及对照组之间差异有统计学意义(P<0.05),OR=1.493,95%CI(1.078~2.068)。11个SNPs位点间无明显连锁关系,各单倍型分析差异无统计学意义。结论TERT基因的rs33963617 SNP位点与宁夏地区人群NSCLP有相关性。

Objective To investigate the association between the single nucleotide polymorphisms of telomerase reverse transcriptase(TERT)gene and non-syndromic cleft lip with or without cleft palate(NSCL/P)in Ningxia population by case-control study.Methods A total of 504 patients with cleft lip and palate patients in the department of oral and maxillofacial surgery were collected.A total of 455 infants(214 males and 241 females)born in the department of obstetrics in the same period were selected as the control group.5 ml of peripheral venous blood were collected from the case group and 5 ml of umbilical cord blood from newborns in the control group was collected.Extraction of genomic DNA.11 tagSNP loci were selected from TERT gene.AgriSeqTM targeted sequencing technique was used for genotyping.Case-control study,linkage analysis and haplotype analysis were used to explore whether the polymorphism of the above genes was associated with NSCLP.Results 11 SNPs loci of rs33954691,rs11133715,rs2736115,rs4246742,rs56345976,rs33963617,rs10069690,rs4975538,rs2736100,rs2853677 and rs2736109 in the control group were in accordance with Harbin-Wen equilibrium.The allele frequency and genotype frequency of rs33963617 SNP locus were significantly different between the case group and the control group(P<0.05),OR=1.493,95%CI(1.078~2.068).There were no significant linkage relationships among 11 SNPs loci,and there were no significant differences among haplotypes.Conclusion The rs33963617 SNP loci of TERT gene is associated with the occurrence of NSCLP in Ningxia population.