Genetic polymorphisms in metabolizing enzymes modifying the association between smoking and inflammatory bowel diseases.
Genetic polymorphisms in metabolizing enzymes modifying the association between smoking and inflammatory bowel diseases.
复制标题
DOI：
10.1097/mib.0000000000000014
复制
发表时间：
2014-05
影响因子：
4.9
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Ananthakrishnan AN;Nguyen DD;Sauk J;Yajnik V;Xavier RJ
吸烟是克罗恩病（CD）和溃疡性结肠炎（UC）的环境危险因素。其作用的确切机制仍未得到解释。代谢酶的遗传多态性可能影响对吸烟影响的易感性，并揭示其作用机制。我们对乳糜泻、UC和健康对照患者进行了前瞻性队列研究。吸烟状况被定义为现在吸烟、曾经吸烟或从不吸烟。使用Sequenom平台对患者进行CYP2A6、谷胱甘肽转移酶（GSTP1和GSTM1）、NAD(P)H醌氧化还原酶（NQO）和血红素加氧酶1多态性的基因分型。建立以CD或UC为结局的多变量logistic回归模型，按基因型分层，并计算相互作用p值。我们的研究包括634名乳糜泻患者，401名UC患者和337名健康对照。在CYP2A6基因型为AG/AA的患者中，与不吸烟者相比，曾经吸烟者患CD的风险增加（OR 3.88, 95% CI 2.35 - 6.39）。然而，在AA基因型患者中，吸烟与乳糜泻无关（p互作0.001）。前吸烟者仅在GSTP1 GG/AG基因型存在时与UC风险增加相关，而在AA基因型存在时与UC风险增加无关（p互作率为0.012）。NQO和HMOX基因座的多态性与吸烟和CD或UC风险之间没有统计学上显著的相互作用。代谢酶的遗传多态性可能影响吸烟与CD和UC之间的关系。对IBD中基因-环境相互作用的进一步研究是必要的。
Cigarette smoking is a well established environmental risk factor for Crohn's disease (CD) and ulcerative colitis (UC). The exact mechanism of its effect remains unexplained. Genetic polymorphisms in metabolizing enzymes may influence susceptibility to the effect of smoking and shed light on its mechanism of action. We utilized a prospective cohort of patients with CD, UC, and healthy controls. Smoking status was defined as current, former, or never smoking. Patients were genotyped for polymorphisms in CYP2A6, glutathione transferase enzymes (GSTP1 and GSTM1), NAD(P)H quinone oxidoreductase (NQO), and Heme Oxygenase 1 using a Sequenom platform. Multivariate logistic regression models with CD or UC as the outcome, stratified by genotype were developed and interaction p-values calculated. Our study included 634 patients with CD, 401 with UC, and 337 healthy controls. Ever smokers had an increased risk of CD (OR 3.88, 95% CI 2.35 – 6.39) compared to non-smokers among patients with AG/AA genotypes at CYP2A6. However, ever smoking was not associated with CD among patients with the AA genotype (pinteraction 0.001). Former smoking was associated with an increased risk for UC only in the presence of GG/AG genotypes for GSTP1, but not in those with the AA genotype (Pinteraction 0.012). Polymorphisms at the NQO and HMOX loci did not demonstrate a statistically significant interaction with smoking and risk of CD or UC. Genetic polymorphisms in metabolizing enzymes may influence the association between smoking and CD and UC. Further studies of gene-environment interaction in IBD are warranted.