Jan Dimberg1, Marie Rubér2, Marita Skarstedt3, Manne Andersson2,4, Roland E Andersson5,6. 1. Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden. 2. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. 3. Department of Laboratory Medicine, Division of Clinical Microbiology, Region Jönköping County, Jönköping, SE 551 85, Sweden. 4. County Hospital Ryhov, Region Jönköping County, Department of Surgery, Jönköping, Sweden. 5. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. roland.andersson@rjl.se. 6. County Hospital Ryhov, Region Jönköping County, Department of Surgery, Jönköping, Sweden. roland.andersson@rjl.se.
Abstract
PURPOSE: The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis. METHODS: As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays. RESULTS: Associations with appendicitis were found for SNPs IL-13 rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17 rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22 rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13 rs1800925 and CTLA4 rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17 rs2275913 and CD44 rs187115. CONCLUSIONS: The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis.
PURPOSE: The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis. METHODS: As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays. RESULTS: Associations with appendicitis were found for SNPs IL-13rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13rs1800925 and CTLA4rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17rs2275913 and CD44 rs187115. CONCLUSIONS: The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis.
Authors: Johanna Gudjonsdottir; Bodil Roth; Gustav Lovén; Bodil Ohlsson; Lars Hagander; Martin Salö Journal: Front Pediatr Date: 2022-05-02 Impact factor: 3.569
Authors: N Kiss; M Minderjahn; J Reismann; J Svensson; T Wester; K Hauptmann; M Schad; J Kallarackal; H von Bernuth; M Reismann Journal: BJS Open Date: 2021-01-08