Genetic Polymorphisms in Metabolizing Enzymes Modifying the Association Between Smoking and Inflammatory Bowel Diseases

被引:34
作者
Ananthakrishnan, Ashwin N. [1 ,2 ]
Nguyen, Deanna D. [1 ,2 ]
Sauk, Jenny [1 ,2 ]
Yajnik, Vijay [1 ,2 ]
Xavier, Ramnik J. [1 ,2 ,3 ,4 ]
机构
[1] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA
[4] Broad Inst, Cambridge, MA USA
基金
美国国家卫生研究院;
关键词
ulcerative colitis; genetics; smoking; Crohn's disease; GLUTATHIONE S-TRANSFERASES; CROHNS-DISEASE; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; NICOTINE METABOLISM; CLINICAL-COURSE; OLMSTED COUNTY; HEAVY SMOKING; LUNG-CANCER; MOIST SNUFF;
D O I
10.1097/MIB.0000000000000014
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: 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. Methods: We used 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. Results: Our study included 634 patients with CD, 401 with UC, and 337 healthy controls. Ever smokers had an increased risk of CD (odds ratio = 3.88, 95% confidence interval = 2.35-6.39) compared with nonsmokers among patients with AG/AA genotypes at CYP2A6. However, ever smoking was not associated with CD among patients with the AA genotype (P-interaction = 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 (P-interaction = 0.012). Polymorphisms at the NQO and HMOX loci did not demonstrate a statistically significant interaction with smoking and risk of CD or UC. Conclusions: Genetic polymorphisms in metabolizing enzymes may influence the association between smoking and CD and UC. Further studies of gene-environment interaction in inflammatory bowel disease are warranted.
引用
收藏
页码:783 / 789
页数:7
相关论文
共 43 条
[1]   MECHANISMS OF DISEASE Inflammatory Bowel Disease [J].
Abraham, Clara ;
Cho, Judy H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (21) :2066-2078
[2]  
Altarescu G, 2011, ISR MED ASSOC J, V13, P87
[3]   Interactions between Diet, Lifestyle and IL10, IL1B, and PTGS2/COX-2 Gene Polymorphisms in Relation to Risk of Colorectal Cancer in a Prospective Danish Case-Cohort Study [J].
Andersen, Vibeke ;
Holst, Rene ;
Kopp, Tine Iskov ;
Tjonneland, Anne ;
Vogel, Ulla .
PLOS ONE, 2013, 8 (10)
[4]   Polymorphisms in the xenobiotic transporter Multidrug Resistance 1 (MDR1) and interaction with meat intake in relation to risk of colorectal cancer in a Danish prospective case-cohort study [J].
Andersen, Vibeke ;
Ostergaard, Mette ;
Christensen, Jane ;
Overvad, Kim ;
Tjonneland, Anne ;
Vogel, Ulla .
BMC CANCER, 2009, 9
[5]   Current smoking differentially affects blood mononuclear cells from patients with crohn's disease and ulcerative colitis: Relevance to its adverse role in the disease [J].
Bergeron, Vivianne ;
Grondin, Virginie ;
Rajca, Sylvie ;
Maubert, Marie-Anne ;
Pigneur, Benedicte ;
Thomas, Ginette ;
Trugnan, Germain ;
Beaugerie, Laurent ;
Cosnes, Jacques ;
Masliah, Joelle ;
Sokol, Harry ;
Seksik, Philippe ;
Bachelet, Maria .
INFLAMMATORY BOWEL DISEASES, 2012, 18 (06) :1101-1111
[6]   Inflammatory bowel disease and smoking -: A review of epidemiology, pathophysiology, and therapeutic implications [J].
Birrenbach, T ;
Böcker, U .
INFLAMMATORY BOWEL DISEASES, 2004, 10 (06) :848-859
[7]   Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms [J].
Bloom, A. Joseph ;
Baker, Timothy B. ;
Chen, Li-Shiun ;
Breslau, Naomi ;
Hatsukami, Dorothy ;
Bierut, Laura J. ;
Goate, Alison .
HUMAN MOLECULAR GENETICS, 2014, 23 (02) :555-561
[8]   Smoking, Use of Moist Snuff, and Risk of Chronic Inflammatory Diseases [J].
Carlens, Cecilia ;
Hergens, Maria-Pia ;
Grunewald, Johan ;
Ekbom, Anders ;
Eklund, Anders ;
Hoglund, Caroline Olgart ;
Askling, Johan .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2010, 181 (11) :1217-1222
[9]   CYP2A6 slow nicotine metabolism is associated with increased quitting by adolescent smokers [J].
Chenoweth, Meghan J. ;
O'Loughlin, Jennifer ;
Sylvestre, Marie-Pierre ;
Tyndale, Rachel F. .
PHARMACOGENETICS AND GENOMICS, 2013, 23 (04) :232-235
[10]  
Cosnes J, 1999, ALIMENT PHARM THERAP, V13, P1403