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©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
Processing time: 102 Days and 21.3 Hours
ARTICLE HIGHLIGHTS
Research background
Genetic factors play an important role in the etiology and nature of inflammatory bowel disease (IBD). Genome-wide association studies and meta-analyses have discovered 230 disease loci linked to IBD and its various phenotypic characteristics. A majority of these studies are conducted among Caucasian populations.
Research motivation
Genetic factors that determine disease patterns are known to vary across different populations and regions. Hence, there is an increased need to study the South Asian population in whom there is only sparse evidence of genetic associations of IBD.
Research objectives
We aimed to study the association of 16 selected single nucleotide polymorphisms (SNPs) in a South Asian multiethnic population of IBD patients in Sri Lanka.
Research methods
A case-control multi-center study was conducted. Patients, who were diagnosed with IBD for over a 1 year duration, were recruited from the four main gastroenterology units in Sri Lanka. A roughly equal number of unrelated gender-matched healthy adult volunteers were recruited. DNA was extracted from peripheral blood, and genotyping was performed for 16 selected SNPs using the Agena MassARRAYay system. Data on disease characteristics including disease behavior, treatment response and severity were obtained. Genotypes of all variants were in Hardy-Weinberg Equilibrium. Data analysis included testing for individual SNPs and various combinations with ulcerative colitis (UC), Crohn’s disease (CD) and different clinical characteristics of these diseases.
Research results
A total of 415 (CD = 158, UC = 258, indeterminate colitis = 4) patients and 465 controls were studied. SNP rs886774 (LAMB1-gene) was associated with UC [odds ratio (OR) = 1.42, P = 0.001]. Other tested mutations failed to demonstrate an association with UC or CD in this population. The following phenotypic associations were noted within the patient population: among UC patients, rs886774 was associated with mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001), and SNP rs10045431 (IL 12B gene) was associated with upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002).
Research conclusions
This study demonstrated the presence of SNP rs886774 (LAMB1-gene) among Sri Lankan patients with UC. Out of the SNPs tested, the majority were not associated with IBD in Sri Lankans. This confirms the genetic heterogeneity of South Asians compared to Caucasian populations.
Research perspectives
Future research should focus on genome-wide association scans and the identification of other genetic risk factors specific to South Asian populations.
