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[细胞色素P450基因多态性(CYP1A1和CYP1A2)与巴什科尔托斯坦慢性阻塞性肺疾病发生的关联]

[Association of cytochrome P450 genes polymorphisms (CYP1A1 and CYP1A2) with the development of chronic obstructive pulmonary disease in Bashkortostan].

作者信息

Korytina G F, Akhmadishina L Z, Kochetova O V, Zagidullin Sh Z, Viktorova T V

出版信息

Mol Biol (Mosk). 2008 Jan-Feb;42(1):32-41.

Abstract

To assess the role that polymorphisms of cytochrome P450 genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of CYPIA1 (2455 A/G, 3801T/C) and CYP1A2 (-2464T/delT, -163C/A) genes were studied in Tatar and Russian COPD patients and in cases of healthy individuals (Russian, Tatar and Bashkir), residents of Bashkortostan. It was shown that the CYP1A1 and CYP1A2 genes haplotypes frequency distribution patterns do not differed between Tatars and Russians ethnic groups (chi2 = 0.973, df = 3, p = 1.00 and chi2 = 1.546, df = 3, p = 0.92, respectively). Analysis of the the CYP1A1 and CYP1A2 genes haplotypes revealed statistically significant differences in the haplotypes frequency distributions between Bashkirs versus Russians and Tatars (chi2 = 12.328, df= 3,p = 0.008; chi2 = 9.218, df=3, p = 0.034, respectively for CYP1A1 gene and (chi2 = 18.779, df=3, p = 0.0001, chi = 14.326, df=3, p = 0.003, respectively for CYP1A2 gene). The (-2467)delT allele and CYP1A21D haplotype of CYPIA2 gene was associated with higher risk of COPD in Tatar ethnic group (OR = 1.83, 95% CI 1.24-2.71, chi2 = 9.48, p = 0.003 and chi2 = 9.733, p = 0.0027, Pcor = 0.008; OR = 3.908, 95% CI 1.56-10.19, respectively). On the other hand the CYP1A21A haplotype had protective effect (chi2 = 6.319, p = 0.0127, Pcor = 0.038; OR = 0.6012, 95% CI 0.402-0.898). But at the same time we did not find any differences in the genotypes and haplotypes frequency distributions of the CYP1A2 gene within the patients and healthy groups in Russian ethnic group. We also did not find any association of CYP1A1 gene with COPD in ethnic groups of Bashkortostan.

摘要

为评估细胞色素P450基因多态性在慢性阻塞性肺疾病(COPD)遗传易感性中所起的作用,我们研究了鞑靼族和俄罗斯族COPD患者以及健康个体(俄罗斯族、鞑靼族和巴什基尔族)中CYPIA1(2455 A/G,3801T/C)和CYP1A2(-2464T/delT,-163C/A)基因的等位基因和基因型分布,这些健康个体均为巴什科尔托斯坦共和国的居民。结果显示,鞑靼族和俄罗斯族群体中CYP1A1和CYP1A2基因单倍型频率分布模式没有差异(卡方值分别为0.973,自由度为3,p = 1.00;卡方值为1.546,自由度为3,p = 0.92)。对CYP1A1和CYP1A2基因单倍型的分析表明,巴什基尔族与俄罗斯族和鞑靼族之间单倍型频率分布存在统计学显著差异(CYP1A1基因的卡方值分别为12.328,自由度为3,p = 0.008;卡方值为9.218,自由度为3,p = 0.034;CYP1A2基因的卡方值分别为18.779,自由度为3,p = 0.0001;卡方值为14.326,自由度为3,p = 0.003)。CYP1A2基因的(-2467)delT等位基因和CYP1A21D单倍型与鞑靼族人群中COPD的较高风险相关(比值比=1.83,95%置信区间1.24 - 2.71,卡方值=9.48,p = 0.003;卡方值=9.733,p = 0.0027,校正p值=0.008;比值比=3.908,95%置信区间1.56 - 10.19)。另一方面,CYP1A21A单倍型具有保护作用(卡方值=6.319,p = 0.0127,校正p值=0.038;比值比=0.6012,95%置信区间0.402 - 0.898)。但同时,我们未在俄罗斯族患者和健康组中发现CYP1A2基因的基因型和单倍型频率分布存在任何差异。我们也未发现巴什科尔托斯坦共和国各民族中CYP1A1基因与COPD存在任何关联。

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