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Genetic associations of inflammatory bowel disease in a South Asian population

World Journal of Clinical Cases 2018年第15期6卷 908-915页

作者： Madunil Anuk Niriella Isurujith Kongala Liyanage senerath kuleesha kodisinghe Arjuna Priyadarsin De Silva Nimna Rajapakshe Sunali D Nanayakkara Dunya Luke Thilakshi Silva Metthananda Nawarathne Ranjith K Peiris Udaya P Kalubovila Sujeewa R Kumarasena Vajira Harshadeva Weerabaddana Dissanayake Rohan W Jayasekara Hithanadura Janaka de Silva Faculty of Medicine University of Kelaniya Faculty of Medical Sciences University of Sri Jayewardenepura University Medical Unit Colombo North Teaching Hospital Gastroenterology Unit National Hospital of Sri Lanka Gastroenterology Unit Colombo South Teaching Hospital Gastroenterology Unit Teaching Hospital Kandy Gastroenterology Unit Teaching Hospital Karapitiya Human Genetics Unit Faculty of Medicine University of Colombo

AIM To estimate prevalence and phenotypic associations of selected inflammatory bowel disease(IBD)-associated genetic variants among Sri Lankan patients. METHODS A case study of histologically confirmed ulcerative colitis(UC) or Crohn's disease(CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12 B :rs1045431, IL23 R :rs11805303, ARPC2 :rs12612347, IRGM :rs13361189, IL26/IL22 :rs1558744, CDH1 :rs1728785, IL10 :rs3024505, FCGR2 A :rs3737240, PTGER4 :rs4613763, IL17 REL/PIM3 :rs5771069, HNF4 a :rs6017342, STAT3 :rs744166, SMURF1 :rs7809799, LAMB1 :rs886774, HLA-DRB5, DQA1, DRB1, DRA :rs9268853, MST1, UBA7, and APEH :rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium(P > 10^(-3)). To account for multiple hypothesis testing, P-values < 0.003 were considered significant.RESULTS A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms(SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774(LAMB1-gene) and UC(odds ratio(OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease(OR = 1.66, P < 0.001) and remained in remission(OR = 1.48, P < 0.001). A positive association was noted between rs10045431(IL 12 B gene) and upper gastrointestinal involvement in CD(OR = 4.76, P = 0.002). CONCLUSION This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.

关键词： Inflammatory bowel disease Genetics of inflammatory bowel disease Ulcerative colitis Crohn’s disease LAMB1 gene mutation IL-12B gene mutation

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