Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome

Dirección de Investigación, Hospital General "Dr. Manuel Gea González", Calzada de Tlalpan 4800, Colonia Sección XVI, 14080 Mexico, DF, Mexico.
Molecular Biology Reports (Impact Factor: 2.02). 06/2012; 39(9):8837-43. DOI: 10.1007/s11033-012-1745-2
Source: PubMed


Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 + 396 G allele (P = 0.02), IL-8 + 396(G/G) and IL-8 + 781(C/T) genotypes (P < 0.001), IL-10 - 1082A allele and IL-10 - 1082(A/A) genotype (P < 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P < 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.

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Available from: Mirza Romero-Valdovinos,
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    • "However, the fecal and serum concentrations of anti-inflammatory cytokine IL-10 was significantly lower in the IBS groups. These results are consistent with previous reports of the levels of these cytokines in sera and mucosal biopsy samples of patients with IBS [31], [32], [33], [34], [35], [36], [37], [38]. "
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    ABSTRACT: Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders, affecting about 20% of the general population in Western countries. This syndrome poses an enormous socio-economic burden, impairs the quality of life substantially, and increases healthcare costs. IBS can be classified as either idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which develops after a bout of acute diarrhea or gastroenteritis. Little is known about the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers in clinical samples of ID-IBS and PI-IBS patients with the goal to test the hypothesis that the immunologic presentations of these forms of IBS are similar, despite their apparent different etiologic origins. Sera and stool samples from PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36 different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit and quantitative ELISA. Our results demonstrated significantly high levels of chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value = 0.003], macrophage inflammatory protein-1β (CCL4) [p-value = 0.010], and CXCL16 (p-value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients. Furthermore, pro-inflammatory cytokines (IFN-γ, IL-1β, and TNF-α) were significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4, and IL-13) were variable except IL-10, which was significantly higher in the healthy volunteers than the IBS patients. Remarkably, the amounts and expression pattern of these biomarkers were not significantly different between ID-IBS and PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical phenotypes, in spite of their different etiologic origins.
    PLoS ONE 03/2014; 9(3):e93144. DOI:10.1371/journal.pone.0093144 · 3.23 Impact Factor
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    ABSTRACT: In Mexico, the initial severe cases of the 2009 influenza pandemic virus A (H1N1) [A(H1N1)pdm09] were detected in early March. The immune mechanisms associated with the severe pneumonia caused by infection with this new virus have not been completely elucidated. Polymorphisms in interleukin genes have previously been associated with susceptibility to infectious diseases due to their influence on cytokine production. The present case-control study was performed to compare several immunologic and genetic parameters of patients and controls during the initial phase of the pandemic. Sixty-five patients who were hospitalized due to infection with the influenza A(H1N1)pdm09 virus and 46 healthy controls were studied. A hemagglutination inhibition assay (HIA) was performed to measure anti-influenza antibody titers in these subjects. Protein levels of the cytokines interleukin (IL)-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), interferon gamma (IFNγ), transforming growth factor beta (TGFβ)1 and TGFβ2 were quantified in plasma. Single nucleotide polymorphisms in IL6, IL10 and TNFα were also assessed. Influenza patients had lower antibody titers and produced significantly higher levels of IL-6, IL-10 and TNFα than healthy controls. The frequencies of the TNFα -308G, IL-10 -592C and IL-10 -1082A alleles and the IL10 -1082(A/A) genotype were associated with susceptibility to severe disease, while the haplotypes TNFα AG and IL-10 GTA and GCA were associated with protection from severe disease [P=0.016, OR (CI)=0.11 (0.01-0.96); P=0.0187, OR (CI)=0.34 (0.13-0.85); P=0.013, OR (CI)=0.39 (0.18-0.83)]. This study demonstrates that the influenza A(H1N1)pdm09 patients and healthy controls have different profiles of immune parameters and that there is an association between IL-10 and TNFα polymorphisms and the outcome of this disease.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2013; 58(1). DOI:10.1016/j.jcv.2013.05.013 · 3.02 Impact Factor
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    ABSTRACT: To clarify the current understanding of the association between interleukin-10 (IL-10) polymorphisms and the risk of irritable bowel syndrome (IBS). We searched for studies in any language recorded in PubMed, Embase and Cochrane library before August 2013. The associations under allele contrast model, codominant model, dominant model, and recessive model were analyzed. The strengths of the association between IL-10 polymorphisms and IBS risk were estimated using odds ratios (OR) with 95% confidence interval (CI). Fixed effects model was used to pool the result if the test of heterogeneity was not significant, otherwise the random-effect model was selected. Eight case-control studies analyzing three single-nucleotide polymorphisms rs1800870 (-1082 A/G), rs1800871 (-819C/T), and rs1800872 (-592A/C) of the IL-10 gene, which involved 928 cases and 1363 controls, were eligible for our analysis. The results showed that rs1800870 polymorphisms were associated with a decreased risk of IBS (GG+GA vs AA: OR = 0.80, 95%CI: 0.66-0.96), (AA+GA vs GG: OR = 0.68, 95%CI: 0.52-0.90). Subgroup analysis revealed such association only existed in Caucasian ethnicity (AA+GA vs GG, OR = 0.70, 95%CI: 0.55-0.89). The rs1800872 polymorphisms were associated with an increased risk of IBS in Asian ethnicity (CC vs GG: OR = 1.29, 95%CI: 1.01-1.16). There were no associations between rs1800871 polymorphisms and the IBS risk. The results suggest that IL-10 rs1800870 confers susceptibility to the risk of IBS in Caucasian ethnicity, and the rs1800872 may associate with IBS risk in Asians. However, no significant associations are found between rs1800871 and IBS risk.
    World Journal of Gastroenterology 12/2013; 19(48):9472-9480. DOI:10.3748/wjg.v19.i48.9472 · 2.37 Impact Factor
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