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 SNPs strongly associated with IBD from GWAS 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 MALDI-ToF 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 8 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.