the tnfsf15 gene single nucleotide polymorphism rs7848647 is associated with surgical diverticulitis objective to determine if single nuclear polymorphisms snps in the tfnsf15 gene play a role in patients requiring surgery for diverticulitisbackground a role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders youthful onset in some patients and the observation of families with multiple affected individuals the tnfsf15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis uc aggressive crohns disease cd and pouchitis after restorative proctocolectomymethods in the discovery phase of this study 21 sporadic surgical diverticulitis sd patients 9 female mean age 52 5 and 5 individuals from a single family with surgically managed diverticulitis familial diverticulitis fd 4 female mean age 511 7 were studied sd patients were age and sex matched with 3 separate groups of healthy cd and uc control patients all patients were genotyped for 5 known tnfsf15associated snps the snp discovered to be associated with diverticulitis rs7848647 was then confirmed in a separate test group composed of 34 additional patients 20 female mean age 577 2 who also underwent surgical treatment for diverticulitis these patients were age matched to a new control cohort of patients having no history of diverticulitis 26 female patients were genotyped using a taqman assay in the discovery phase logistical regression on matched subjects was performed to determine an association of tnfsf snp with diverticulitis versus the control groups in the test phase significance for the rs7848647 snp was assessed by the fischers exact testresults in the discovery phase the tnfsf15 snp rs7848647 was significantly associated with sd p 00003 versus all control groups studied the risk allele for this snp g substituted for a was found in all sd patients the homozygous gg allele was found in 62 1321 of sd patients versus only 5 121 of healthy controls p 0001 and 24 1042 of all uc cd controls p 0002 all 5 members of the fd cohort were homozygous for the atrisk g allele in the test group the homozygous gg genotype was found in 56 of sd patients compared with 17 of healthy controls p 0006 risk of sd seemed to increase with number of the g alleles with 8 of sd patients having aa homozygosity 35 of sd patients having ag heterozygosity and 56 of sd patients having gg homozygosityconclusions the snp rs7848647 associated with the tnfsf15 gene is associated with surgical diverticulitis this finding suggests a fundamental role for tnfsf15 a tcell receptor gene involved in tcell maturation in the pathophysiology of diverticulitis requiring surgery this snp may be a marker of diverticular disease severity that might assist in surgical decision making