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

Baskaran K, Pugazhendhi S, Ramakrishna BS - PLoS ONE (2014)

Bottom Line: 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.Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632 004, India.

ABSTRACT

Background: Tumor 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.

Methods: Seven 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.

Results: The 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.

Conclusions: Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.

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Related in: MedlinePlus

LD pattern between Five TNFSF15 SNPs. rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 were in tight LD (D′ = 0.76–0.99) and were organized in single haplotype block.
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pone-0114665-g001: LD pattern between Five TNFSF15 SNPs. rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 were in tight LD (D′ = 0.76–0.99) and were organized in single haplotype block.

Mentions: Initially only five of the seven genotyped SNPs (rs38910936, rs6478108, rs6478109, rs7848647 & rs7869487) were used to construct six haplotypes (A–F) (Table 3, Fig. 1). All the 5 SNPs were organized in a single haplotype block. However LD among four SNPs (rs6478108, rs6478109, rs7848647 & rs7869487) was almost complete (D′ ranging from 0.92 to 0.99), while rs3810936 was in weak LD with rest of the four SNPs (D′ ranging from 0.76 to 0.82), The haplotype block structure of the five SNPs is shown in Table 3. Estimation of haplotype frequencies were done in case and controls separately in order to characterize the haplotypes of these five polymorphisms. Haplotype A, containing the risk alleles of all five SNPs, was significantly associated with IBD (Table 4). The carrier frequency for haplotype A was 0.66 in CD and 0.65 in UC, and was significantly less (0.60) in controls (P = 0.01 and 0.03 for CD and UC respectively). On the other hand, haplotype C had a protective association with IBD, with a frequency of 0.08 in CD and 0.09 in UC compared to 0.12 in controls (P = 0.02 for CD and 0.03 for UC). The remaining haplotypes were devoid of significant differences in their frequencies between cases and controls.


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

Baskaran K, Pugazhendhi S, Ramakrishna BS - PLoS ONE (2014)

LD pattern between Five TNFSF15 SNPs. rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 were in tight LD (D′ = 0.76–0.99) and were organized in single haplotype block.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264777&req=5

pone-0114665-g001: LD pattern between Five TNFSF15 SNPs. rs3810936, rs6478108, rs6478109, rs7848647, rs7869487 were in tight LD (D′ = 0.76–0.99) and were organized in single haplotype block.
Mentions: Initially only five of the seven genotyped SNPs (rs38910936, rs6478108, rs6478109, rs7848647 & rs7869487) were used to construct six haplotypes (A–F) (Table 3, Fig. 1). All the 5 SNPs were organized in a single haplotype block. However LD among four SNPs (rs6478108, rs6478109, rs7848647 & rs7869487) was almost complete (D′ ranging from 0.92 to 0.99), while rs3810936 was in weak LD with rest of the four SNPs (D′ ranging from 0.76 to 0.82), The haplotype block structure of the five SNPs is shown in Table 3. Estimation of haplotype frequencies were done in case and controls separately in order to characterize the haplotypes of these five polymorphisms. Haplotype A, containing the risk alleles of all five SNPs, was significantly associated with IBD (Table 4). The carrier frequency for haplotype A was 0.66 in CD and 0.65 in UC, and was significantly less (0.60) in controls (P = 0.01 and 0.03 for CD and UC respectively). On the other hand, haplotype C had a protective association with IBD, with a frequency of 0.08 in CD and 0.09 in UC compared to 0.12 in controls (P = 0.02 for CD and 0.03 for UC). The remaining haplotypes were devoid of significant differences in their frequencies between cases and controls.

Bottom Line: 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.Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.

View Article: PubMed Central - PubMed

Affiliation: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632 004, India.

ABSTRACT

Background: Tumor 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.

Methods: Seven 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.

Results: The 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.

Conclusions: Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.

Show MeSH
Related in: MedlinePlus