In recent times, some common "non-pathogenic" parasites, such as Blastocystis and Dientamoeba fragilis, have been associated to the aetiology of irritable bowel syndrome (IBS), while host pro-inflammatory cytokine gene polymorphisms might have a role in the pathophysiology of the disease. Therefore, Blastocystis subtypes (ST), D. fragilis and gene promoter single nucleotide polymorphisms of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in IBS patients and controls were studied. After giving written consent, 45 patients with symptoms of IBS according to the Rome III criteria and 45 controls were enrolled. DNA was extracted from peripheral blood for SNP analysis at position -174 for IL-6 as well as -238 and -308 for TNF-α. Blastocystis was more common in the IBS group (p = 0.043). Interestingly, D. fragilis was found more frequently in the control group (p = 0.002); Blastocystis ST1 and 3 were most frequent in both groups. Haploview analysis revealed linkage disequilibrium in TNF-α (p < 0.0001); however, none of the SNPs for IL-6 and TNF-α were found to be significantly related with IBS. The clinical and molecular approaches undertaken for the first time in Latin American IBS patients demonstrated an association with Blastocystis that supports a pathogenic role of this parasite in IBS Furthermore, co-infections with ST1 and ST3 were frequent; thus, the genetic diversity proposed within ST polymorphisms does not rule out that particular strains might be associated with disease. In addition, our results do not support a major contribution of IL-6 and TNF-α gene polymorphisms in the susceptibility to IBS.

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Key Messages• To date genetic association studies on immunogenic genes have been performed in irritable bowel syndrome by various groups mainly working with small case-control samples.• We did an exercise trying to replicate previous findings in two case-control samples of similar size of earlier studies. We performed genotyping of 16 previously analyzed SNPs residing in genes involved in immune response followed by a meta-analysis taking this and earlier studies into account.• None of the SNPs was found to be associated in our samples. • Although powerful in combining effect size of single studies, the meta-analysis did not show any positive finding except for a moderate association of rs4263839 in TNFSF15.• The major issues with current genetics studies in IBS are low statistical power and large heterogeneity of IBS. In addition, the main focus of the recruiting centre may bias for enrolling certain entities of patients.• Large well characterized patient and control samples recruited by harmonized criteria are mandatory in order to overcome these limitations. AbstractBackground To date, genetic-association studies of single nucleotide polymorphisms (SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome (IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk. Methods We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry.

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.

The intestinal protozoan parasite Blastocystis is one of the most common parasites worldwide in humans and, although its ability to cause human disease has been questioned, some reports have demonstrated that this microorganism is associated to the development of irritable bowel syndrome (IBS) and to a proinflammatory response, in which the expression of some cytokines is unregulated. Since inflammatory cytokine gene polymorphisms might have a role in the pathophysiology of IBS, we assessed the role of single nucleotide polymorphisms (SNPs) for interleukin (IL)-8 and IL-10, in previously collected DNA samples from IBS patients and controls, with or without Blastocystis infection. IL-8+396(G) and IL-10-1082 (A) alleles (p=0.0437 and p=0.0267, respectively), as well as their homozygous (p<0.0001 and p=0.0039, respectively) and IL-8+781(CT) (p=0.0248) genotypes were significantly overrepresented in patients with IBS in comparison with controls. IL-8+396(GG) genotype was relevant because it was associated to IBS (p<0.0001), to Blastocystis (p=0.0025), and to IBS–Blastocystis (p=0.0272). In the latter binomial association, this genotype presented a high contribution (etiological fraction =0.452) and a risk >fourfold to develop IBS. IL-8+781 (T) and IL-10-592 (C) alleles were also associated to Blastocystis and to IBS–Blastocystis, respectively (p=0.0448 and p=0.0166). Our results suggest that some IL-8 and IL-10 SNPs could change individual susceptibility increasing the relative risk in the development of IBS in Blastocystis carriers.

B-2b.

Background: The purpose of this study was to assess the genetic variation and differentiation of Blastocystis subtypes (STs) recovered from symptomatic children by analysing partial sequences of the small subunit rDNA gene region (SSUrDNA) and internal transcribed spacers (1 and 2) plus the 5.8S region (ITS, ITS1 + 5.8S + ITS2) and comparing with isolates from other countries.

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