Protective Association of Tumor Necrosis Factor Superfamily 15 (TNFSF15) Polymorphic Haplotype with Ulcerative Colitis and Crohn's Disease in an Indian Population

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.

Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East

“…However, only 5 SNPs, namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2), and rs2066843 (NOD2), retained significance after Bonferroni correction. Another Indian study reported a strong protective association with TNFSF15 (tumour necrosis factor superfamily) gene polymorphisms and IBD in the Indian population [39] . TNFSF15 has also been associated with an IBD risk in studies from Japan and the UK [40,41] .…”

Identification of Two Additional Susceptibility Loci for Inflammatory Bowel Disease in a Chinese Populationy

“…Moreover, many TL1A loci are associated with IBD susceptibility across all ethnic and age groups [11, 15, 16]. rs10114470 is a novel TL1A locus that was found to provide significant protection against both CD and UC in an Indian population [17]. However, the relationship between rs1250569, rs1042522, and rs10114470 variants and IBD susceptibility has not yet been investigated in a Chinese population.…”

High throughput characterization of genetic effects on DNA:protein binding and gene transcription

“…We found 2,054 Cen-tiSNPs with ASB (p-value<0.05) and 1,769 CentiSNPs with ASE (p-value<0.05) associated to a complex trait in the GWAS catalog (Table S5,S6) or with a PPA>0.1 from fgwas [12]. We were able to dissect the molecular mechanism for rs3810936, a variant associated with risk for Crohn s disease in multiple populations [40,41,42,43] (Figure 3e,f). This variant is a CentiSNP for the factor Hmx3 (Nkx5-1) and we find ASB for NFKB (p-value=0.006) in the BiT-BUNDLE-seq assay and ASE (p-value=0.034) in both directions in the BiT-STARR-seq.…”

“…BiT-STARR-seq z score is the z score from meta-analysis of ASE for nine experimental replicates. GWAS OR is the odds ratio from rs3810936 alternate allele with Crohns disease [40,41,42,43]. All scores are signed relative to the risk allele, which is the alternate allele.…”