Genetic polymorphisms of ATG16L1 and IRGM genes in Malaysian patients with Crohn's disease

• Published in: Journal of digestive diseases 2020-01, Vol.21 (1), p.29-37
• Main Authors: Kee, Boon Pin, Ng, Jin Guan, Ng, Ching Ching, Hilmi, Ida, Goh, Khean Lee, Chua, Kek Heng
• Format: Article
• Language: English
• Subjects: Alleles; Arthritis; ATG16L1; Autophagy; Chloroform; Crohn disease; Crohn's disease; Gene polymorphism; genetic polymorphism; Genotype & phenotype; Genotyping; Ileum; Inflammation; IRGM; Phagocytosis; Phenols; Polymorphism; Population; Population genetics; Single-nucleotide polymorphism
• ISSN: 1751-2972; 1751-2980
• DOI: 10.1111/1751-2980.12829

Objective To investigate the association between genetic polymorphisms in ATG16L1 and IRGM genes and the development of Crohn's disease (CD) in Malaysian patients. Methods Altogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol‐chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy‐Weinberg equilibrium were also calculated. Results Two SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race‐stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD. Conclusion We found a significant association between SNP, which are located in autophagy‐related genes, and CD in a Malaysian population.