Background: Previous studies conducted in various geographical and ethnical populations have shown that Alpha-1-antitrypsin (Alpha-1-AT) expression affects the occurrence and progression of chronic obstructive pulmonary disease (COPD). We aimed to explore the associations of rs9944155AG, rs1051052AG, and rs1243166AG polymorphisms in the Alpha-1-AT gene with the risk of COPD in Uygur population in the Kashgar region.
Methods: From March 2013 to December 2015, a total of 225 Uygur COPD patients and 198 healthy people were recruited as cases and controls, respectively, in Kashgar region. DNA was extracted according to the protocol of the DNA genome kit, and Sequenom MassARRAY single-nucleotide polymorphism technology was used for genotype determination. Serum concentration of Alpha-1-AT was detected by enzyme-linked immunosorbent assay. A logistic regression model was used to estimate the associations of polymorphisms with COPD.
Results: The rs1243166-G allele was associated with a higher risk of COPD (odds ratio [OR] = 2.039, 95% confidence interval [CI]: 1.116-3.725, P = 0.019). In cases, Alpha-1-AT levels were the highest among participants carrying rs1243166 AG genotype, followed by AA and GG genotype (χ2 = 11.89, P = 0.003). Similarly, the rs1051052-G allele was associated with a higher risk of COPD (OR = 19.433, 95% CI: 8.783-43.00, P < 0.001). The highest Alpha-1-AT levels were observed in cases carrying rs1051052 AA genotype, followed by cases with AG and GG genotypes (χ2 = 122.45, P < 0.001). However, individuals with rs9944155-G allele exhibited a lower risk of COPD than those carrying the rs9944155-A allele (OR = 0.121, 95% CI: 0.070-0.209, P < 0.001). In both cases and controls, no significant difference in Alpha-1-AT levels was observed among various rs9944115 genotypes.
Conclusions: rs1243166, rs9944155, and rs1051052 sites of Alpha-1-AT may be associated with the COPD morbidity in Uygur population. While rs1243166-G allele and rs1051052-G allele are associated with an increased risk of developing COPD, rs9944155-G allele is a protect locus in Uygur population. Alpha-1-AT levels in Uygur COPD patients were lower than those in healthy people and differed among patients with different rs1051052 AG and rs1243166 AG genotypes.
喀什地区维吾尔族人群α1抗胰蛋白酶基因位点rs9944155、rs1051052和rs1243166基因多态性与慢性阻塞性肺疾病的关系摘要背景: 以往研究表明在不同种族、不同人群中，α-1-抗胰蛋白酶(Alpha-1-AT)的表达影响慢性阻塞性肺疾病(COPD)的发生和发展。我们研究的目的是探讨新疆维吾尔族人群中α-1-抗胰蛋白酶基因rs9944155AG、rs1051052AG、rs1243166AG多态性与COPD发病的关系。 方法: 选取2013年3月至2015年12月喀什地区第一人民医院（新疆维吾尔自治区，中国）住院收治的225例维吾尔族COPD患者作为病例组,根据成组匹配的原则(年龄，性别）收集198例维吾尔族健康体检人群作为对照组，用DNA试剂盒提取DNA，利用Sequenom MassARRAY SNP技术对α1-抗胰蛋白酶基因多态性分析，采用酶联免疫吸附试验(ELISA)检测血清α-1-抗胰蛋白酶水平。 结果: rs1243166-G等位基因与COPD的发病风险有关(OR=2.039, 95%CI: 1.116-3.725, P =0.019)。在病例组中，携带rs1243166 AG基因型的患者α-1-AT水平较高，AA和GG基因型比较低 (χ2 = 11.89, P = 0.003)。同样，rs1051052-G等位基因有较高的患病风险 (OR = 19.433, 95% CI: 8.783-43.00, P <0.001)。rs1051052 AA 基因型α-1-抗胰蛋白酶水平较高， AG 和 GG基因型α-1-抗胰蛋白酶水平较低 (χ2 =122.45, P <0.001)。然而，携带rs9944155-G等位基因的个体患COPD的风险低于携带rs9944155-A等位基因(OR = 0.121, 95% CI: 0.070-0.209, P <0.001)。在病例组和对照组中，rs 9944115不同基因型之间α-1-抗胰蛋白酶水平差异无统计学意义。 结论: α1-抗胰蛋白酶基因rs1243166，rs9944155和rs1051052位点可能与维吾尔族COPD的发病有关，维吾尔族人群携带rs1243166-G等位基因、携带rs1051052-G等位基因可能有较高的患病风险。rs9944155-G等位基因是维吾尔族COPD的保护基因。CODP患者α-1-抗胰蛋白酶水平低于健康对照组，在病例组中rs1051052-AG基因型和rs1243166-AG 基因型对应的α-1-抗胰蛋白酶水平也不同。.
Keywords: Alpha-1-antitrypsin; Chronic Obstructive Pulmonary Disease; Polymorphism; Uygur Population.