Effect of the interleukin 10 polymorphisms on interleukin 10 production and visceral hypersensitivity in Chinese patients with diarrhea-predominant irritable bowel syndrome

Abstract

Background: Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is characterized by cytokine imbalance. Previously, decreased plasma interleukin 10 (IL-10) level was reported in patients with IBS, which may be due to genetic polymorphisms. However, there are no reports correlating the IL-10 polymorphisms with IL-10 production in patients with IBS. This study aimed to analyze the effect of IL-10 polymorphisms on IL-10 production and its correlation with the clinical symptoms in Chinese patients with diarrhea-predominant IBS (IBS-D). Methods: Two IL-10 single nucleotide polymorphisms ( rs1800871 and rs1800896 ) were detected in 120 patients with IBS-D and 144 healthy controls (HC) using SNaPshot. IBS symptom severity score, Bristol scale, hospital anxiety, and depressive scale (HADS) were used to evaluate the clinical symptoms, as well as the psychological status and visceral sensitivity of the subjects. IL-10 levels in the plasma and peripheral blood mononuclear cell (PBMC) culture supernatant were measured using enzyme-linked immunosorbent assay, while those in ileal and colonic mucosal biopsies were measured using immunohistochemistry. Results: The frequency of rs1800896 C allele was significantly lower in the patients with IBS-D than that in the HC (odds ratio: 0.49, 95% confidence interval: 0.27–0.92, P = 0.0240). The IL-10 levels in the plasma ( P = 0.0030) and PBMC culture supernatant ( P = 0.0500) of the CT genotype subjects were significantly higher than those in the TT genotype subjects. The CT genotype subjects exhibited a higher pain threshold in the rectal distention test than the TT genotype subjects. Moreover, IL-10 rs1800871 GG genotype subjects showed an increase in the HADS score compared to other genotype subjects. Conclusions: IL-10 rs1800896 C allele is correlated with higher IL-10 levels in the plasma and the PBMC culture supernatant, which is associated with a higher pain threshold in the Chinese patients with IBS-D. This study provides an explicit relationship of IL-10 polymorphisms with IL-10 production, which might help in understanding the pathogenesis of IBS-D.

Genetic associations and potential mediators between psychiatric disorders and irritable bowel syndrome: a Mendelian randomization study with mediation analysis

“…Abnormal levels of cytokines, including TNF-α, IL-8, and IL-10, are significantly associated with IBS and bipolar disorder symptoms, indicating that IBS and bipolar disorder share similar pathophysiological mechanisms ( 75 – 79 ). Thus, the comorbidity of both disorders was hypothesized.…”

Evaluation of the Impact of Some Single-Nucleotide Gene Polymorphisms on the Development of Adenomatous Polyps of the Colon in Patients with Irritable Bowel Syndrome

“…We confirmed the influence of genetic SNPs on the development of IBS and the formation of ADPC concomitant with IBS, which is in concordance with the data of other researchers. 16 , 22 , 24 , 25 The investigated genetic SNP often had a combined effect on the diseases, affecting both the emergence of IBS and adenomatous polyps concomitant with IBS. The pronounced influence of polymorphic variations on the development of the diseases responsible for the functioning of pro-inflammatory and anti-inflammatory cytokines, reparative properties of the CM, and stability of the intestinal microbiome has been noted, which is in concordance with the findings of other authors.…”

“… 12 - 14 It is reported that SNPs are responsible for the functioning of cytokines in the human body and have the most significant impact on the development of ADPC and IBS. Interleukin (IL)-1β (rs1143627, rs 16944), 4 , 11 Interleukin IL6 (rs1800795), 13 - 16 Interleukin IL10 (rs1800872, rs1800871, rs1800896) 12 , 13 , 15 , 16 are distinguished among the SNPs, which could potentially have an impact on the disease considering their influence on dysbiosis and on changes in the colon epithelium that is caused by deviation of gene expression.…”