Genetic variants involved in innate immunity modulate the risk of inflammatory bowel diseases in an understudied Malaysian population

Luu LDW 1 , Popple G 1 , Tsang SPW 1 , Vinasco K 1 , Hilmi I 2 , Ng RT 3 Show all authors , Chew KS 3 , Wong SY 3 , Riordan S 4 , Lee WS 3 , Mitchell HM 1 , Kaakoush NO 5 , Castaño-Rodríguez N 1

Affiliations 

  • 1 School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia
  • 2 Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 3 Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 4 Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, New South Wales, Australia
  • 5 School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
J Gastroenterol Hepatol, 2022 Feb;37(2):342-351.
PMID: 34888949 DOI: 10.1111/jgh.15752

Abstract

BACKGROUND AND AIM: Inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory conditions comprising two major subtypes: Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is increasing in Asian countries including Malaysia. The aim of this study was to determine whether 32 single nucleotide polymorphisms (SNPs) strongly associated with IBD from genome-wide association studies, performed mainly in Caucasian populations, are associated with IBD in a Malaysian population, correlating these findings with local and systemic inflammation.

METHODS: Selected SNPs were investigated in a Malaysian cohort comprising 36 IBD patients and 75 controls using customized matrix-assisted laser desorption ionization time-of-flight genotyping. Local mRNA and/or systemic protein levels of IL-10, IL-12, IL-22, IL-23, and TNF-α were measured in these same subjects.

RESULTS: ATG16L2 rs11235667 and LINC00824 rs6651252 was significantly associated with increased CD risk while IL12B rs56167332 was a significant protective factor. Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor. After adjusting for age, gender, and ethnicity, SBNO2 rs2024092, ATG16L2 rs11235667, CARD9 rs10781499, and LINC00824 rs6651252 remained associated with IBD. Interestingly, the risk alleles of IL10 rs3024505, CARD9 rs1078149, and IL12 rs6556412 were associated with higher levels of IL-10, IL-22, and IL-23 in these same subjects, respectively.

CONCLUSIONS: This study identified eight SNPs associated with IBD and/or its subtypes in the Malaysia population, significantly advancing our understanding of the genetic contribution to IBD in this understudied population. Three of these SNPs modulated relevant cytokine levels and thus, may directly contribute to IBD pathogenesis.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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