Background and aim: Tobacco smoking is a risk factor for gastrointestinal disorders, causing mucosal damage and impairing immune responses. However, smoking has been found to be protective against ulcerative colitis (UC). Human leukocyte antigen (HLA) is a major susceptibility locus for UC, and HLA-DRB1*15:02 has the strongest effect in Asians. This study investigated the effects of smoking on the association between HLA and UC.
Methods: The study enrolled 882 patients with UC, including 526 never, 151 current, and 205 former smokers, and 3091 healthy controls, including 2124 never, 502 current, and 465 former smokers. Smoking-stratified analyses of HLA data were performed using a case-control approach.
Results: In a case-control approach, HLA-DRB1*15:02 was associated with UC in never smokers (ORnever smokers = 3.20, Pnever smokers = 7.88 × 10-23 ) but not in current or former smokers (Pcurrent smokers = 0.72 and Pformer smokers = 0.33, respectively). In current smokers, HLA-DQB1*06 was associated with UC (ORcurrent smokers = 2.59, Pcurrent smokers = 6.39 × 10-12 ). No variants reached genome-wide significance in former smokers.
Conclusions: An association between UC and HLA-DRB1*15:02 was limited to never smokers. Our findings highlight that tobacco smoking modifies the effects of HLA on the risk of UC.
Keywords: HLA; gene-environment interaction; smoking; ulcerative colitis.
© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.