Association of the FBX011 gene with chronic otitis media with effusion and recurrent otitis media -: The Minnesota COME/ROM Family Study
Association of the FBX011 gene with chronic otitis media with effusion and recurrent otitis media -: The Minnesota COME/ROM Family Study
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DOI：
10.1001/archotol.132.7.729
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发表时间：
2006-07-01
影响因子：
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通讯作者：
Bowden, Donald W.
中科院分区：
文献类型：
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作者：
Segade, Fernando;Daly, Kathleen A.;Bowden, Donald W.
目的：FBXO 11基因是一种新的耳聋小鼠突变体jeff（Jf）中突变基因的人类同源基因。我们已经评估了FBXO 11基因的单核苷酸多态性（SNP）与慢性渗出性中耳炎/复发性中耳炎（COME/ROM）的相关性。设计：在包含FBXO 11的基因组DNA的98，7个碱基中，共对13个SNP进行基因分型。使用广义估计方程分析单个SNP关联的数据，使用系谱不平衡检验方法评估单倍型。患者：明尼苏达COME/ROM家族研究，一组142个家族（619名受试者）与多个患有COME/ROM的个体的研究。主要结果测量：COME/ROM与FBXO 11多态性的遗传关联。FBXO11单核苷酸多态性包含在一个单一的连锁不平衡单倍型块。13个SNP中的10个在样品中具有足够的多态性以允许分析。在单变量遗传分析中，1个参考SNP（下文称为rs）（rs2134056）显示与COME/ROM相关的名义证据（P =.02），并且2个SNP接近显著性（rs2020911，P =.06; rs3136367，P =.05）。09）。在多变量分析中，包括已知的COME/ROM风险因素（性别、吸烟暴露、参加日托中心、既往未母乳喂养和过敏），每个SNP的独立关联证据减少（例如，rs2134056，从P = 0.02到P = 0.08）。在随后使用系谱不平衡检验的分析中，FBXO 11 SNP rs2134056（P =.06）与COME/ROM的关联被证实。在2-和3-位点SNP单倍型中发现了多个SNP，那些含有rs2134056的单倍型也显示了FBXO 11与COME/ROM相关的证据（P值范围为0.03至0.05）。10）.结论：我们观察到的证据与FBXO 11（Jeff小鼠模型基因的人类同源物）多态性和COME/ROM之间的关联一致。
Objective: The FBXO11 gene is the human homologue of the gene mutated in the novel deaf mouse mutant jeff (Jf), a single gene model of otitis media. We have evaluated single nucleotide polymorphisms (SNPs) in the FBXO11 gene for association with chronic otitis media with effusion/recurrent otitis media (COME/ROM).Design: A total of 13 SNPs were genotyped across the 98,7 kilobases of genomic DNA encompassing FBXO11. Data were analyzed for single SNP association using generalized estimating equations, and haplotypes were evaluated using Pedigree Disequilibrium Test methods.Patients: The Minnesota COME/ROM Family Study, a group of 142 families (619 subjects) with multiple affected individuals with COME/ROM.Main Outcome Measures: Genetic association of COME/ROM with polymorphisms in FBXO11.Results: The FBXO11 SNPs are contained in a single linkage disequilibrium haplotype block. Ten of the 13 SNPs were sufficiently polymorphic in the sample to permit analysis. In univariate genetic analysis, 1 reference SNP (hereinafter rs) (rs2134056) showed nominal evidence of association to COME/ROM (P=.02), and 2 SNPs approached significance (rs2020911, P=.06; rs3136367, P =. 09). In multivariable analyses, including known risk factors for COME/ROM (sex, exposure to smoking, attending day care centers, no prior breastfeeding, and having allergies), the evidence of independent association was reduced for each SNP (eg, rs2134056, from P=.02 to P =.08). In subsequent analyses using the Pedigree Disequilibrium Test, the association of FBXO11 SNP rs2134056 (P =.06) with COME/ROM was confirmed. Incorporating multiple SNPs in 2- and 3-locus SNP haplotypes, those haplotypes containing rs2134056 also exhibited evidence of association of FBXO11 and COME/ ROM (P values ranging from .03 to. 10).Conclusion: We have observed evidence consistent with an association between polymorphisms in FBXO11, the human homologue of the Jeff mouse model gene, and COME/ROM.