摘要
目的:探讨IL-13基因启动子-1055C/T、外显子+2044A/G、内含子+1923C/T 3个位点的SNPs与新疆维吾尔族人群COPD易感性的关系。方法:采用病例-对照研究方法,以新疆和田地区确诊为COPD的220例60岁以上维吾尔族稳定期患者为病例组,对照组为220例年龄、性别与病例组相匹配的、无血缘关系的该地区维吾尔族无COPD者。采集静脉血并收集各项检查指标。用全血DNA提取试剂盒提取静脉血中基因组DNA,应用聚合酶链反应(PCR)法扩增目的片段,DNA测序法进行单核苷酸多态性(SNPs)鉴定。用SPSS17.0软件进行统计学分析。用SHEsis软件进行连锁不平衡及单倍型分析。结果:(1)IL-13基因启动子-1055C/T位点,病例组和对照组CC、CT、TT基因型的频率分布比较χ2=14.185,P<0.05;C、T等位基因的频率分布比较χ2=16.055,P<0.05。Logistic回归分析,CT基因型对CC基因型的优势比OR值为2.155(95%Cl:1.286-3.614),TT基因型对CC基因型的优势比OR值为2.705(95%Cl:1.103-6.634)。(2)IL-13基因外显子+2044G/A位点,病例组和对照组GG、GA、AA基因型的频率分布比较χ2=1.518,P>0.05;G、A等位基因的频率分布比较χ2=0.880,P>0.05。(3)IL-13基因内含子+1923C/T位点,病例组和对照组CC、CT. TT基因型的频率分布比较χ2=3.191,P>0.05;C、T等位基因的频率分布比较χ2=1.410,P>0.05。(4)IL-13基因启动子-1055C/T、外显子+2044A/G、内含子+1923C/T3个SNPs两两之间不存在连锁不平衡。(5)3个SNPs位点构成8种单倍型,其中3种单倍型的频率分布在病例组与对照组中有统计学差异。结论:IL-13基因启动子-1055C/T位点SNPs与维吾尔族COPD发生有关;外显子+2044G/A位点SNPs与维吾尔族COPD发生不相关;内含子+1923C/T位点SNPs与维吾尔族COPD发生不相关。3个SNPs两两之间不存在连锁不平衡。3种单倍型可能与新疆维吾尔族人群COPD相关。
Objective:To study the association between polymorphism of IL-13 gene promoter-1055C/T, exon+2044A/G, intron+1923C/T and susceptibility to chronic obstructive pulmonary disease in Xinjiang Uyger population. Methods:220 stable COPD patients (the case group) and healthy controls (the control group) of 220 age-and-sex matched with the case group, unrelated individuals were recruited in a case-control study to the Uygur of Hetian region. The venous blood and the check index were collected. Whole blood genomic DNA were extracted, DNA fragment was amplified by Polymerase chain reaction (PCR), DNA sequencing were identified by single nucleotide polymorphism (SNPs) cation. Data were analysised by SPSS 17.0 software. LD and haplotype were analysised by SHEsis software. Results:(1) For IL-13 gene promoter-1055C/T locus, comparison of genotype frequency distribution of CC, CT and TT isχ2=14.185 and P<0.05 in case group and control groups; Comparison of allele frequency distribution of C and T isχ2=16.055, P<0.05; In Logistic regression analysis, OR of CT genotype vs CC genotype is 2.155(95%CI:1.286-3.614), OR of TT genotypes vs CC genotype is 2.705(95%CI:1.103-6.634). (2) For IL-13 exon+2044G/A locus, comparison of genotype frequency distribution of GG, GA and AA isχ2=1.518 and P>0.05 in case group and control groups; Comparison of allele frequency distribution of G and A isχ2=0.880 and P >0.05. (3) For IL-13 gene intron+1923C/T locus, comparison of genotype frequency distribution of CC, CT and TT isχ2=3.191and P>0.05 in case group and control groups; Comparison of allele frequency distribution of C and T isχ2=1.410 and P>0.05. (4) Pairwise LD analysis found there were no linkage disequilibrium in three SNPs. (5) Three SNPs loci constitute 8 haplotypes, and three haplotypes frequency distribution in the case group and control group were significantly different. Conclusion:The genetic polymorphism in promoter-1055C/T locus of IL-13 was associated with the susceptibility to COPD in Xinjiang Uyger population. The genetic polymorphism in Exon +2044G/A locus of IL-13 was not associated with the susceptibility to COPD in Xinjiang Uyger population. The genetic polymorphism in Intron+1923C/T locus of IL-13 was not associated with the susceptibility to COPD in Xinjiang Uyger population. There were no linkage disequilibrium in three SNPs. Three haplotypes may be associated with COPD in Xinjiang Uygur population.
引文
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