Rs531564 polymorphism in microRNA-214 regulates interleukin-6R expression in anal fissure patients to affect the risk of anal abscess formation.

BACKGROUND: Anal abscess is an important complication of anal fissure (AF), whereas interleukin-6R (IL-6R) has been implicated in the development of abscess. In this study, we aimed to explore the possible molecular mechanisms underlying the regulatory effects of miRNAs on IL-6R and other inflammatory factors related to the induction of anal abscess in AF. METHODS: Bioinformatics analysis, luciferase assay, real-time polymerase chain reaction, and Western blot analysis were performed to identify the possible regulatory relationships between IL-6R and miR-124/miR-125a by comparing the differentiated expression of miR-125a, miR-124, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and IL-4 among different groups of AF patients. RESULTS: IL-6R messenger RNA (mRNA) was identified as a target gene of miR-124 because the luciferase activity in cells cotransfected with wild-type IL-6R and miR-124 mimics was significantly reduced. In addition, the expression of IL-6R mRNA and protein was significantly inhibited in the presence of miR-124 or an IL-6R inhibitor, confirming the presence of a negative regulatory relationship between miR-124 and IL-6R. Moreover, miR-124 and inflammatory factors were differentially expressed in AF patients carrying different genotypes of rs531564 polymorphism. CONCLUSIONS: miR-124 and inflammatory factors TNF-α, IFN-γ, and IL-4 may be used as indicators of anal abscess development in AF patients. In addition, miR-124 polymorphism rs531564 is involved with the pathogenesis of anal abscess in AF patients, and the presence of rs531564 may increase the incidence of anal abscess via upregulating the expression of IL-6R, TNF-α, IFN-γ, and IL-4.

Mutation in TAGAP is protective of anal sepsis in ileocolic Crohn's disease.

BACKGROUND: Anal complications of Crohn's disease range from painless skin tags to debilitating fistulas that are imperfectly treated with tumor necrosis factor antagonists. The recent discovery of more than 190 single-nucleotide polymorphisms associated with Crohn's disease offers the opportunity to genetically define the severity of anal disease in Crohn's disease and possibly predict prognosis and anti-tumor necrosis factor response. OBJECTIVES: This study aimed to identify single nucleotide polymorphisms associated with anal disease generally, septic anal disease specifically and the responsivity to anti-tumor necrosis factor treatment. DESIGN: All patients with ileocolonic Crohn's disease were identified from our IBD registry. One hundred ninety-six Crohn's disease-related single-nucleotide polymorphisms were analyzed by the use of a custom microarray chip. Patients' response to anti-tumor necrosis factor treatment was then assessed. RESULTS: One hundred sixteen patients with ileocolonic Crohn's disease were identified and assigned to septic anal disease (abscesses/fistulas, n = 35), benign anal disease (skin tags/fissures/isolated pain, n = 17), and no anal disease (n = 64) cohorts. Single-nucleotide polymorphism rs212388 negatively correlated with the presence of anal disease overall and septic disease specifically. The presence of the non-wild-type allele 'G' was protective of anal sepsis with homo- and heterozygotes having a 75% chance of no anal disease (p = 0.0001). The homozygous wild-type group had the highest risk of septic disease and included 3 of 4 patients requiring diverting ileostomies. Twenty-four patients were treated with anti-tumor necrosis factors. Nine had a beneficial response (assessed at >6 months); however, no single-nucleotide polymorphism correlated with anti-tumor necrosis factor response. Rs212388 is associated with the TAGAP molecule involved in T-cell activation. CONCLUSIONS: Rs212388 most significantly correlated with the presence and severity of anal disease in ileocolonic Crohn's disease. A single copy of the risk allele was protective, whereas wild-type homozygotes had the highest risk of septic disease and stoma creation. In this select group, no single-nucleotide polymorphism was predictive of anti-tumor necrosis factor response. Mutations in TAGAP may predict a more benign form and course of anal disease in Crohn's disease.

Anal human papillomavirus infection: a comparative study of cytology, colposcopy and DNA hybridisation as methods of detection.

OBJECTIVE: To compare anal cytology, colposcopy and DNA hybridisation as methods of detecting anal HPV infection. SUBJECTS AND DESIGN: Patients attending: (1) a genitourinary medicine (GUM) clinic with ano-genital warts; (2) a surgical out-patient department with anal fissure or haemorrhoids were examined for evidence of anal HPV infection. RESULTS: Considering GUM clinic attenders, 17% (38/225) and 40% (90/225) had perianal or anal canal warts respectively. Colposcopic examination revealed anal acetowhite lesions without warts in 28% (63/225). Cytological evidence of HPV infection was found in 98%, 83%, and 90% of patients with anal canal warts, perianal warts and acetowhite lesions respectively. Anal intraepithelial neoplasia (AIN) was documented in 22% of patients with anal canal warts compared with 6% with perianal warts (p less than 0.01). HPV DNA was detected from the anal brushings of 71%, 50%, 32%, and 29% of patients with anal canal warts, perianal warts, acetowhite lesions and a normal anal examination respectively. HPV type 6/11 was detected in the majority of HPV positive samples. Considering surgical out-patient attenders with no history or signs of anal warts, 25% showed cytological evidence of anal HPV infection and HPV DNA was detected from anal brushings in 3% (2/71). CONCLUSION: Anal examination with the colposcope is a useful method for detecting subclinical HPV infection. Anal cytology may prove helpful for detecting AIN, however, since koilocytosis was rarely seen, the specificity of the cytological criteria for anal HPV infection in the absence of AIN is uncertain. DNA analysis of anal brushings proved only moderately sensitive.