Protective association of tumor necrosis factor superfamily 15 (TNFSF15) polymorphic haplotype with Ulcerative Colitis and Crohn's disease in an Indian population.

Kirankumar Baskaran,Balakrishnan S Ramakrishna,Srinivasan Pugazhendhi,Mathias Chamaillard

doi:10.1371/journal.pone.0114665

Kirankumar Baskaran, Balakrishnan S Ramakrishna + Show 2 more

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https://doi.org/10.1371/journal.pone.0114665

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Abstract

BackgroundTumor necrosis factor superfamily (TNFSF) proteins are involved in the genesis of inflammatory bowel disease (IBD). We examined the association of seven single nucleotide polymorphisms (SNP) in the TNFSF15 gene with Crohn's disease (CD) and ulcerative colitis (UC) in the Indian population.MethodsSeven SNPs in the TNFSF15 gene (rs10114470, rs3810936, rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487) were genotyped in 309 CD patients, 330 UC patients and 437 healthy controls using the Sequenom iPLEX MassArray platform. Disease associations were evaluated for allelotypes and for genotypes.ResultsThe minor T alleles and the TT genotypes of rs10114470 and rs3810936 were significantly protectively associated with both CD and UC. The CC genotype of rs6478108, AA genotype of rs4263839, the AA genotype of rs6478109, the TT genotype of rs7848647 and the CC genotype of rs7869487 were all protectively associated with CD but not with UC. Two haplotype blocks could be discerned, one where SNPs rs10114470 and rs3810936 were in tight LD (D′ = 0.8) and the other where rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487 were in tight LD (D′ 0.92–1.00). The second block of haplotypes were not associated with CD or with UC. The first block of haplotypes was very significantly associated with both CD and UC.ConclusionsStrong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.

Highlights

The inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by chronic inflammation of the intestine and/or colon resulting from complex gene-environment interactions [1]
We examined the association of seven single nucleotide polymorphisms (SNP) in the Tumor Necrosis Factor Superfamily 15 (TNFSF15) gene with Crohn’s disease (CD) and ulcerative colitis (UC) in the Indian population
An increased expression level of TNFSF15 in intestinal lamina propria cells correlated with the degree of intestinal inflammation in CD [31]

Summary

Introduction

The inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by chronic inflammation of the intestine and/or colon resulting from complex gene-environment interactions [1]. Studies in South Asian migrants to the United Kingdom and North America indicate that incidence and prevalence of IBD in second generation migrants approaches or exceeds that in the local population [5,6,7]. The genetic background that permits development of IBD is complex, probably involves multiple genes that each confer a relatively small increase in risk of IBD, and characterized by population specific differences. The nucleotide-binding oligomerization domain 2 (NOD2) was the first gene to be identified as conferring susceptibility to CD. We examined the association of seven single nucleotide polymorphisms (SNP) in the TNFSF15 gene with Crohn’s disease (CD) and ulcerative colitis (UC) in the Indian population. Conclusions: Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population

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