BACKGROUND AND AIM: Ulcerative colitis (UC) and Crohn's disease (CD) are two major phenotypes of inflammatory bowel disease (IBD) that present with inflammation of the colon or the entire gastrointestinal tract, respectively. Genome-wide association studies have confirmed the role of nucleotide-binding oligomerization domain protein-2 (NOD2) variants and identified several other genes associated with IBD. We investigated whether variants in NOD2 and interleukin-23 receptor (IL23R) are associated with IBD in a well-characterized case-control cohort from southern India. METHODS: We recruited 652 patients (411 UC and 241 CD) using established diagnostic criteria and 442 age-, sex-, and ethnically-matched, normal individuals. By direct sequencing, we screened the complete NOD2 gene and genotyped the R381Q variant in IL23R, and performed an association analysis and genotype-phenotype correlation analysis. RESULTS: The clinical presentation of UC and CD patients did not differ significantly from the Europeans. We observed a monomorphic status for three common disease-susceptible variants, R702W, G908R, and 1007fs in NOD2; three other single nucleotide polymorphisms, P268S, R459R, and R587R, had a comparable minor allele frequency in patients and controls. Compared to Europeans, we found a low frequency (∼1%) of the protective allele at R381Q in IL23R and no statistically-significant association with IBD (odds ratio = 0.87; 95% confidence interval = 0.26-2.86; P>0.05). CONCLUSIONS: Our study suggests that variants in the NOD2 gene and the protective variant R381Q in IL23R are not associated with IBD in Indians. Additional variants in these or other candidate genes might play a major role in the pathophysiology of IBD in Indians.
BACKGROUND AND AIM: Ulcerative colitis (UC) and Crohn's disease (CD) are two major phenotypes of inflammatory bowel disease (IBD) that present with inflammation of the colon or the entire gastrointestinal tract, respectively. Genome-wide association studies have confirmed the role of nucleotide-binding oligomerization domain protein-2 (NOD2) variants and identified several other genes associated with IBD. We investigated whether variants in NOD2 and interleukin-23 receptor (IL23R) are associated with IBD in a well-characterized case-control cohort from southern India. METHODS: We recruited 652 patients (411 UC and 241 CD) using established diagnostic criteria and 442 age-, sex-, and ethnically-matched, normal individuals. By direct sequencing, we screened the complete NOD2 gene and genotyped the R381Q variant in IL23R, and performed an association analysis and genotype-phenotype correlation analysis. RESULTS: The clinical presentation of UC and CDpatients did not differ significantly from the Europeans. We observed a monomorphic status for three common disease-susceptible variants, R702W, G908R, and 1007fs in NOD2; three other single nucleotide polymorphisms, P268S, R459R, and R587R, had a comparable minor allele frequency in patients and controls. Compared to Europeans, we found a low frequency (∼1%) of the protective allele at R381Q in IL23R and no statistically-significant association with IBD (odds ratio = 0.87; 95% confidence interval = 0.26-2.86; P>0.05). CONCLUSIONS: Our study suggests that variants in the NOD2 gene and the protective variant R381Q in IL23R are not associated with IBD in Indians. Additional variants in these or other candidate genes might play a major role in the pathophysiology of IBD in Indians.
Authors: David Prescott; Charles Maisonneuve; Jitender Yadav; Stephen J Rubino; Stephen E Girardin; Dana J Philpott Journal: Proc Natl Acad Sci U S A Date: 2020-04-29 Impact factor: 11.205
Authors: Balakrishnan S Ramakrishna; Govind K Makharia; Vineet Ahuja; Uday C Ghoshal; Venkataraman Jayanthi; Benjamin Perakath; Philip Abraham; Deepak K Bhasin; Shobna J Bhatia; Gourdas Choudhuri; Sunil Dadhich; Devendra Desai; Bhaba Dev Goswami; Sanjeev K Issar; Ajay K Jain; Rakesh Kochhar; Goundappa Loganathan; Sri Prakash Misra; C Ganesh Pai; Sujoy Pal; Mathew Philip; Anna Pulimood; Amarender S Puri; Gautam Ray; Shivaram P Singh; Ajit Sood; Venkatraman Subramanian Journal: Indian J Gastroenterol Date: 2015-03-14
Authors: Zhenwu Lin; John P Hegarty; Gerrit John; Arthur Berg; Zhong Wang; Rishabh Sehgal; Danielle M Pastor; Yunhua Wang; Leonard R Harris; Lisa S Poritz; Stefan Schreiber; Walter A Koltun Journal: Dig Dis Sci Date: 2013-05-26 Impact factor: 3.199