Dataset Information

Association of TLR5 gene polymorphisms in ulcerative colitis patients of north India and their role in cytokine homeostasis.

ABSTRACT:

Background and aim

In health, TLR signaling protects the intestinal epithelial barrier and in disease, aberrant TLR signaling stimulates diverse inflammatory responses. Association of TLR polymorphisms is ethnicity dependent but how they impact the complex pathogenesis of IBD is not clearly defined. So we propose to study the status of polymorphisms in TLR family of genes and their effect on cytokines level in UC patients.

Methods

The genotypes of the six loci TLR1-R80T, TLR2-R753Q, TLR3-S258G, TLR5-R392X, TLR5-N592S and TLR6-S249P were determined in 350 controls and 328 UC patients by PCR-RFLP and sequencing. Cytokine levels were measured by ELISA in blood plasma samples. Data were analyzed statistically by SPSS software.

Results

TLR5 variants R392X and N592S showed significant association (p = 0.007, 0.021) with UC patients but TLR 1, 2, 3, 6 variants did not show any association. Unlike other studies carried out in different ethnic groups, TLR 6 (S249P) SNP was universally present in our population irrespective of disease. Genotype-phenotype correlation analysis revealed that the patients having combination of multiple SNPs both in TLR5 and TLR4 gene suffered from severe disease condition and diagnosed at an early age. The level of TNF? (p = 0.004), IL-6 (p = 0.0001) and IFN? (p = 0.006) significantly increased in patients as compared to controls having wild genotypes for the studied SNPs. However, there was decreased level of TNF? (p = 0.014), IL-6 (p = 0.028) and IFN? (p = 0.001) in patients carrying TLR5-R392X variant as compared to wild type patients. Patients carrying two simultaneous SNPs D299G in TLR4 gene and N592S in TLR5 gene showed significant decrease in the levels of TNF? (p = 0.011) and IFN? (p = 0.016).

Conclusion

Polymorphisms in TLR 5 genes were significantly associated with the UC in North Indian population. The cytokine level was significantly modulated in patients with different genotypes of TLR4 and TLR5 SNPs.

SUBMITTER: Meena NK

PROVIDER: S-EPMC4366177 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Association of TLR5 gene polymorphisms in ulcerative colitis patients of north India and their role in cytokine homeostasis.

Meena Naresh Kumar NK Ahuja Vineet V Meena Kusumlata K Paul Jaishree J

PloS one 20150319 3

<h4>Background and aim</h4>In health, TLR signaling protects the intestinal epithelial barrier and in disease, aberrant TLR signaling stimulates diverse inflammatory responses. Association of TLR polymorphisms is ethnicity dependent but how they impact the complex pathogenesis of IBD is not clearly defined. So we propose to study the status of polymorphisms in TLR family of genes and their effect on cytokines level in UC patients.<h4>Methods</h4>The genotypes of the six loci TLR1-R80T, TLR2-R753 ...[more]

PMID: 25789623

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Dataset Information

Association of TLR5 gene polymorphisms in ulcerative colitis patients of north India and their role in cytokine homeostasis.

Background and aim

Methods

Results

Conclusion

Publications

Association of TLR5 gene polymorphisms in ulcerative colitis patients of north India and their role in cytokine homeostasis.

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