Sex-stratified linkage analysis identifies a female-specific locus for IgE to cockroach in Costa Ricans
Sex-stratified linkage analysis identifies a female-specific locus for IgE to cockroach in Costa Ricans
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DOI：
10.1164/rccm.200711-1697oc
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发表时间：
2008-04-15
影响因子：
24.7
通讯作者：
Celedon, Juan C.
中科院分区：
文献类型：
--
作者：
Hunninghake, Gary M.;Lasky-Su, Jessica;Celedon, Juan C.
性别对过敏原特异性IgE影响的基础尚不清楚。目的：对三种过敏原的IgE进行定期和性别分层的全基因组连锁分析（蛔虫、德国小蠊（Blatella germanica）和屋尘螨（Dermatophagoides pteronyssinus）[尘螨]），并对连锁基因组区域中的候选基因进行关联研究。对哥斯达黎加8个哮喘患儿大家庭的653名成员进行了过敏原特异性IgE的全基因组连锁分析。在哥斯达黎加的417个亲子三人组中进行了胸腺基质淋巴细胞生成素（TSLP）单核苷酸多态性与IgE测量之间的关联分析。在儿童哮喘管理项目（CAMP.Measurements and Main Results）中，在470个白色儿童家庭中重复了显著结果：在所有受试者中，有提示性证据表明IgE与蛔虫（染色体7 q）和IgE与尘螨（染色体7 p和12 q）存在连锁（LOD >= 2.72）。在性别分层分析中，有显着的证据表明，在女性受试者的染色体5q23（峰值LOD，4.14，在127 cM）上与蟑螂的IgE连锁。TSLP位于该连锁峰的1.5 LOD单位支持区间内，对小鼠肺部疾病具有雌性特异性影响。在性别分层分析中，TSLP单核苷酸多态性rs2289276的T等位基因与蟑螂IgE（哥斯达黎加女孩）和总IgE（哥斯达黎加女孩和CAMP）的降低相关，性别与基因型相互作用的P值，
Rationale The basis for gender influences on allergen-specific IgEs is unclear.Objectives: To perform regular and sex-stratified genomewide linkage analyses of IgE to each of three allergens (Ascaris lumbricoides, Blatella germanica [German cockroach]), and Dermatophagoides pteronyssinus [dust mite]) and to conduct an association study of a candidate gene in a linked genomic region.Methods: Genomewide linkage analyses of allergen-specific IgEs were conducted in 653 members of eight large families of Costa Rican children with asthma. An analysis of the association between single-nucleotide polymorphisms in thymic stromal lymphopoietin (TSLP) and IgE measurements was conducted in 417 parent-child trios in Costa Rica. Significant results were replicated in 470 families of white children in the Childhood Asthma Management Program (CAMP).Measurements and Main Results: Among all subjects, there was suggestive evidence of linkage (LOD >= 2.72) to IgE to Ascaris (on chromosome 7q) and IgE to dust mite (on chromosomes 7p and 12q). In a sex-stratified analysis, there was significant evidence of linkage to IgE to cockroach on chromosome 5q23 (peak LOD, 4.14 at 127 cM) in female subjects. TSLP is located within the 1.5 LOD-unit support interval for this linkage peak and has female-specific effects on lung disease in mice. In a sex-stratified analysis, the T allele of single-nucleotide polymorphism rs2289276 in TSLP was associated with reductions in IgE to cockroach (in Costa Rican girls) and total IgE (in girls in Costa Rica and in CAMP, P value for sex-by-genotype interaction,