Otitis media: a genome-wide linkage scan with evidence of susceptibility loci within the 17q12 and 10q22.3 regions.

BACKGROUND: Otitis media (OM) is a common worldwide pediatric health care problem that is known to be influenced by genetics. The objective of our study was to use linkage analysis to map possible OM susceptibility genes. METHODS: Using a stringent diagnostic model in which only those who underwent tympanostomy tube insertion at least once for recurrent/persistent OM are considered affected, we have carried out a genome-wide linkage scan using the 10K Affymetrix SNP panel. We genotyped 403 Caucasian families containing 1,431 genotyped individuals and 377 genotyped affected sib pairs, and 26 African American families containing 75 genotyped individuals and 27 genotyped affected sib pairs. After careful quality control, non-parametric linkage analysis was carried out using 8,802 SNPs. RESULTS: In the Caucasian-only data set, our most significant linkage peak is on chromosome 17q12 at rs226088 with a p-value of 0.00007. Other peaks of potential interest are on 10q22.3 (0.00181 at rs1878001), 7q33 (0.00105 at rs958408), 6p25.1 (0.00261 at rs554653), and 4p15.2 (0.00301 at rs2133507). In the combined Caucasian and African American dataset, the 10q22.3 peak becomes more significant, with a minimal p-value of 0.00026 at rs719871. Family-based association testing reveals signals near previously implicated genes: 513 kb from SFTPA2 (10q22.3), 48 kb from IFNG (12q14), and 870 kb from TNF (6p21.3). CONCLUSION: Our scan does not provide evidence for linkage in the previously reported regions of 10q26.3 and 19q13.43. Our best-supported linkage regions may contain susceptibility genes that influence the risk for recurrent/persistent OM. Plausible candidates in 17q12 include AP2B1, CCL5, and a cluster of other CCL genes, and in 10q22.3, SFTPA2.

Eustachian tube function as a predictor of the recurrence of middle ear effusion in children.

OBJECTIVES/HYPOTHESIS: In children with ventilation tubes (VTs) inserted for chronic otitis media with effusion (COME), the authors sought to determine whether any parameter of Eustachian tube (ET) function measured by the forced response test (FRT) predicts disease recurrence after the VT becomes nonfunctional. STUDY DESIGN: Prospective study of those factors that predict disease recurrence in children with VTs inserted for COME. METHODS: Forty-nine subjects (73 ears; 28 male, 34 white, aged 5.3 ± 1.2 years) with COME had VTs inserted and were evaluable for disease status after the VT(s) became nonfunctional. The FRT was done when the VTs were patent, and results for the last test before the VT became nonfunctional were used in the analysis. After each VT became nonfunctional, the children were followed for disease recurrence over a 12-month period. Logistic regression was used to determine whether the ET opening pressure, closing pressure, and/or dilatory efficiency predicted disease recurrence. That model was expanded to include age, sex, race, history of adenoidectomy, previous VTs, and duration of VT patency as potential predictive factors. RESULTS: Twenty-nine (40%) ears had recurrence of significant disease within 12 months after the VT became nonfunctional. For the complete logistic regression model, male gender (P = .03), nonwhite race (P = .02), shorter period of VT patency (P = .01), and low dilatory efficiency (P = .01) were significant predictors of disease recurrence. CONCLUSIONS: A measure of active ET function, dilatory efficiency, but not measures of passive function predicted disease recurrence within the 12 months after the VT became nonfunctional in children with COME.