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A case-only study of gene-environment interaction between genetic susceptibility variants in NOD2 and cigarette smoking in Crohn's disease aetiology

DOI: 10.1186/1471-2350-13-14

Keywords: Gene-environment interaction, Case-only, Crohn's disease, NOD2/CARD15, Cigarette smoking

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Abstract:

Three previously reported CD-associated variants in NOD2 (R702W, G908R, 1007fs) were genotyped in 1636 patients with CD continuously recruited between 1995 and 2010 based on physician referral. Data on history of smoking behaviour was obtained for all participants through a written questionnaire. Using a case-only design, we performed logistic regression analyses to investigate statistical interactions between NOD2 risk alleles and smoking status.We detected a significant negative interaction between carriership of at least one of the NOD2 risk alleles and history of ever having smoked (OR = 0.71; p = 0.005) as well as smoking at the time of CD diagnosis (OR = 0.68; p = 0.005). Subsequent separate analyses of the three variants revealed a significant negative interaction between the 1007fs variant and history of ever having smoked (OR = 0.64; p = 9 × 10-4) and smoking at the time of CD diagnosis (OR = 0.53; p = 7 × 10-5).The observed significant negative gene-environment interaction suggests that the risk increase for CD conferred simultaneously by cigarette smoking and the 1007fs NOD2 polymorphism is smaller than expected and may point to a biological interaction. Our findings warrant further investigation in epidemiological and functional studies to elucidate pathophysiology as well as to aid in the development of recommendations for disease prevention.Crohn's disease (CD) is a common form of inflammatory bowel disease (IBD) characterised by chronic relapsing and remitting episodes of transmural inflammation of the gastrointestinal tract. High rates of CD are found in North America (including Canada), northern Europe, and the United Kingdom, with an estimated 47,000 new cases diagnosed each year in North America and 41,000 new cases diagnosed each year in Europe [1]. The disease burden of CD is high, often associated with complications such as intestinal strictures, fistulas, and granulomas, the need for surgical intervention, and extraintestinal manifestations [2

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