Luu, Laurence Don Wai and Popple, Georgia and Tsang, Samuel Pok Wei and Vinasco, Karla and Hilmi, Ida and Ng, Ruey Terng and Chew, Kee Seang and Wong, Shin Yee and Riordan, Stephen and Lee, Way Seah and Mitchell, Hazel M. and Kaakoush, Nadeem O. and Castano-Rodriguez, Natalia (2022) Genetic variants involved in innate immunity modulate the risk of inflammatory bowel diseases in an understudied Malaysian population. Journal of Gastroenterology and Hepatology, 37 (2, SI). pp. 342-351. ISSN 0815-9319, DOI https://doi.org/10.1111/jgh.15752.
Full text not available from this repository.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-alpha 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.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Malaysia [Grant No: UM.C/625/HIR/MOHE/CHAN/13/1], Cancer Institute NSW Early Career Fellowship, Ministry of Education, Malaysia [Grant No: UM.C/625/HIR/MOHE/CHAN/13/1], Cancer Institute NSW [Grant No: 2019/ECF1082], University of New South Wales, Foundation for the Future of Colombia Colfuturo |
| Uncontrolled Keywords: | Crohn's disease; Immunogenetics; Inflammatory bowel diseases; Innate immunity; Ulcerative colitis |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 22 Jul 2022 02:42 |
| Last Modified: | 22 Jul 2022 02:42 |
| URI: | http://eprints.um.edu.my/id/eprint/33639 |
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