Copyright
©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Genetic associations of inflammatory bowel disease in a South Asian population
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
Madunil Anuk Niriella, Arjuna Priyadarsin De Silva, Nimna Rajapakshe, Sunali D Nanayakkara, Dunya Luke, Thilakshi Silva, Hithanadura Janaka de Silva, Faculty of Medicine, University of Kelaniya, Ragama GQ 10110, Sri Lanka
Isurujith Kongala Liyanage, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda 10250, Sri Lanka
Senerath Kuleesha Kodisinghe, University Medical Unit, Colombo North Teaching Hospital, Ragama 0025, Sri Lanka
Metthananda Nawarathne, Gastroenterology Unit, National Hospital of Sri Lanka, Colombo 0010, Sri Lanka
Ranjith K Peiris, Gastroenterology Unit, Colombo South Teaching Hospital, Kalubovila 80000, Sri Lanka
Udaya P Kalubovila, Gastroenterology Unit, Teaching Hospital Kandy, Kandy 20400, Sri Lanka
Sujeewa R Kumarasena, Gastroenterology Unit, Teaching Hospital Karapitiya, Galle 80000, Sri Lanka
Vajira Harshadeva Weerabaddana Dissanayake, Rohan W Jayasekara, Human Genetics Unit, Faculty of Medicine, University of Colombo, Colombo 0010, Sri Lanka
Author contributions: Niriella MA, de Silva HJ and Jayasekara RW conceptualized the study design; Liyanage IK, Kodisinghe SK, De Silva AP, Rajapakshe N, Nanayakkara SD, Luke D and Silva T were researchers involved in data collection, analysis and preparation of this manuscript; Nawarathne M, Peiris RK, Kalubovila UP and Kumarasena SR assisted with providing access to consenting patients from their respective units; Liyanage IK carried out the data analysis under the supervision of Niriella MA, De Silva AP, Dissanayake VH, Jayasekara RW and de Silva HJ who were overall supervisors leading data acquisition, analysis and formulation of this manuscript; Dissanayake VH was the lead of the genetics analysis; all authors read and accepted the final version of this manuscript.
Supported by National Research Council, Sri Lanka, Grant No. NRC 13-108.
Institutional review board statement: Ethical approval for the study was obtained from the Ethical Review Committee (ERC) of the Faculty of Medicine, University of Kelaniya and Hospital ERCs where relevant.
Informed consent statement: Informed written consent was obtained from all participants of this study.
Conflict-of-interest statement: All authors declare that there are no conflicts of interest.
Data sharing statement: Data was made anonymous after the initial data entry and cleaning process. Data was stored securely with access only limited to the investigators. Data was only used for the purpose of this study.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Madunil Anuk Niriella, MBBS, MD, MRCP, FRCP, Professor, Department of Clinical Medicine, Faculty of Medicine, University of Kelaniya, Ragama GQ 10110, Sri Lanka. maduniln@yahoo.co.uk
Telephone: +94-714820948 Fax: +94-112958337
Received: August 27, 2018
Peer-review started: August 27, 2018
First decision: October 9, 2018
Revised: October 29, 2018
Accepted: November 7, 2018
Article in press: November 7, 2018
Published online: December 6, 2018
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: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a: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 12B 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.
Core tip: This is a case-control study looking at the prevalence of genetic mutations, ones that are commonly associated with inflammatory bowel disease (IBD) among Caucasians, in a South Asian population from Sri Lanka. Most allelic variants studied were not seen in this population, confirming the heterogeneity of the genetic composition of IBD between South Asians and Caucasian patients. We found positive associations between rs886774 (LAMB1-gene) and ulcerative colitis, which was also associated with a milder disease and increased remission rate. Patients with upper gastrointestinal involvement of Crohn’s disease were more likely to have the mutation rs10045431 (IL 12B gene).
