A case-only study of gene-environment interaction between genetic susceptibility variants in <it>NOD2 </it>and cigarette smoking in Crohn's disease aetiology
<p>Abstract</p> <p>Background</p> <p>Genetic variation in <it>NOD2 </it>and cigarette smoking are well-established risk factors for the development of Crohn's disease (CD). However, little is known about a potential interaction between these risk factor...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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BMC,
2012-03-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Genetic variation in <it>NOD2 </it>and cigarette smoking are well-established risk factors for the development of Crohn's disease (CD). However, little is known about a potential interaction between these risk factors. We investigated gene-environment interactions between CD-associated <it>NOD2 </it>alleles and cigarette smoking in a large sample of patients with CD.</p> <p>Methods</p> <p>Three previously reported CD-associated variants in <it>NOD2 </it>(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 <it>NOD2 </it>risk alleles and smoking status.</p> <p>Results</p> <p>We detected a significant negative interaction between carriership of at least one of the <it>NOD2 </it>risk alleles and history of ever having smoked (OR = 0.71; <it>p </it>= 0.005) as well as smoking at the time of CD diagnosis (OR = 0.68; <it>p </it>= 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; <it>p </it>= 9 × 10<sup>-4</sup>) and smoking at the time of CD diagnosis (OR = 0.53; <it>p </it>= 7 × 10<sup>-5</sup>).</p> <p>Conclusions</p> <p>The observed significant negative gene-environment interaction suggests that the risk increase for CD conferred simultaneously by cigarette smoking and the 1007fs <it>NOD2 </it>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.</p> |
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| Item Description: | 10.1186/1471-2350-13-14 1471-2350 |