Department of Human Genetics, University of Debrecen, Debrecen, Hungary.
BMC Med Genet. 2010 Nov 2;11:152. doi: 10.1186/1471-2350-11-152.
In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease.
Two proposed casual single nucleotide polymorphisms (SNP) (rs1051740, rs2234922) in microsomal epoxide hydrolase (EPHX1) and three SNPs (rs1801282, rs1800571, rs3856806) in peroxisome proliferator-activated receptor gamma (PPARG), a new candidate gene, were genotyped in a case-control study (272 COPD patients and 301 controls subjects) in Hungary. Allele frequencies and genotype distributions were compared between the two cohorts and trend test was also used to evaluate association between SNPs and COPD. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested in logistic regression analysis. Association between haplotypes and COPD outcome was also assessed.
The distribution of imputed EPHX1 phenotypes was significantly different between the COPD and the control group (P = 0.041), OR for the slow activity phenotype was 1.639 (95% CI = 1.08- 2.49; P = 0.021) in our study. In logistic regression analysis adjusted for both variants, also age and pack-year, the rare allele of His447His of PPARG showed significant association with COPD outcome (OR = 1.853, 95% CI = 1.09-3.14, P = 0.0218). In haplotype analysis the GC haplotype of PPARG (OR = 0.512, 95% CI = 0.27-0.96, P = 0.035) conferred reduced risk for COPD.
The "slow" activity-associated genotypes of EPHX1 were associated with increased risk of COPD. The minor His447His allele of PPARG significantly increased; and the haplotype containing the minor Pro12Ala and the major His447His polymorphisms of PPARG decreased the risk of COPD.
除了吸烟之外，遗传易感性被认为在慢性阻塞性肺疾病（COPD）的发病机制中起着重要作用。对 COPD 新候选基因的遗传关联研究可能会导致对疾病发病机制的更好理解。
在匈牙利的一项病例对照研究（272 例 COPD 患者和 301 例对照受试者）中，对微粒体环氧化物水解酶（EPHX1）中的两个拟议的因果单核苷酸多态性（SNP）（rs1051740、rs2234922）和过氧化物酶体增殖物激活受体γ（PPARG）中的三个 SNP（rs1801282、rs1800571、rs3856806）进行了基因分型。比较了两组之间的等位基因频率和基因型分布，并进行了趋势检验以评估 SNP 与 COPD 之间的关联。为了估计关联强度，计算了比值比（OR）（95%CI），并在 logistic 回归分析中测试了潜在的混杂变量。还评估了单体型与 COPD 结局之间的关联。
EPHX1 表型的分布在 COPD 组和对照组之间存在显著差异（P=0.041），在我们的研究中，慢活性表型的 OR 为 1.639（95%CI=1.08-2.49；P=0.021）。在调整了两个变体（也包括年龄和吸烟包年）后进行 logistic 回归分析时，PPARG 的 His447His 稀有等位基因与 COPD 结局显著相关（OR=1.853，95%CI=1.09-3.14，P=0.0218）。在单体型分析中，PPARG 的 GC 单体型（OR=0.512，95%CI=0.27-0.96，P=0.035）降低了 COPD 的风险。
EPHX1 的“慢”活性相关基因型与 COPD 的风险增加相关。PPARG 的较小 His447His 等位基因显著增加；并且包含较小的 Pro12Ala 和较大的 His447His 多态性的 PPARG 单体型降低了 COPD 的风险。
