RESUMO
OBJECTIVE: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. BACKGROUND: 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 Crohn's disease (CD), and pouchitis after restorative proctocolectomy. METHODS: 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 = 51.1 ± 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 TNFSF15-associated 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 57.7 ± 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 Fischer's exact test. RESULTS: In the discovery phase, the TNFSF15 SNP rs7848647 was significantly associated with SD (p = 0.0003) 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% (13/21) of SD patients versus only 5% (1/21) of healthy controls (p = 0.001) and 24% (10/42) of all UC + CD controls (p = 0.002). All 5 members of the FD cohort were homozygous for the at-risk "G" allele. In the test group, the homozygous GG genotype was found in 56% of SD patients compared with 17% of healthy controls (p = 0.006). 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 homozygosity. CONCLUSIONS: The SNP rs7848647 associated with the TNFSF15 gene is associated with surgical diverticulitis. This finding suggests a fundamental role for TNFSF15, a T-cell receptor gene involved in T-cell 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.
Assuntos
Colectomia/métodos , Doenças do Colo/genética , DNA/genética , Diverticulite/genética , Polimorfismo de Nucleotídeo Único , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Idoso , Alelos , Doenças do Colo/cirurgia , Diverticulite/cirurgia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Estudos RetrospectivosRESUMO
BACKGROUND: We aimed to determine if an increased incidence of incisional hernias is present in patients undergoing sigmoidectomy for diverticulitis vs cancer. The pathophysiology of diverticulitis is poorly understood, but might involve a collagen vascular abnormality that can predispose to incisional hernia. STUDY DESIGN: In this IRB-approved, retrospective study, patients who underwent sigmoid colectomies for diverticulitis or cancer between January 2003 and September 2012 were studied. Exclusion criteria included the development of surgical site infections and neoadjuvant chemoradiotherapy. A multivariate logistic regression was used with covariate adjustments for known risk factors for hernia development. RESULTS: Four hundred forty-two patients (mean age 59.3 ± 13.9 years) with a median follow-up of 30 months were analyzed. The incidence of incisional hernia was 15.1% in diverticulitis patients vs 5.8% in the cancer cohort (41 of 271 vs 10 of 171; p = 0.003). Univariate analysis of risk factors associated with postoperative incisional hernia included steroid use (p = 0.007), wound packing (p = 0.001), higher American Society of Anesthesiologists classification (p = 0.001), absorbable suture closure (p = 0.02), blood transfusion (p = 0.04), stoma formation (p = 0.02), increased body mass index (p = 0.008), and history of incisional hernia (p = 0.00008). Multivariate logistic regression demonstrated a persistent association between diverticulitis and hernia development (p = 0.01). Odds of a hernia developing after sigmoidectomy for diverticulitis were 2.82 times greater than in the cancer cohort (95% CI, 1.3-6.6). CONCLUSIONS: The incidence of an incisional hernia developing after a sigmoid colectomy is significantly higher when performed for diverticulitis as compared with cancer. This might be due to a connective tissue disorder, which predisposes to development of both diverticula and hernias.