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使用子代对中亲回归(ROMP)方法研究哮喘患者对热带嗜碱螨致敏遗传性中的性别差异。

Sex differences in heritability of sensitization to Blomia tropicalis in asthma using regression of offspring on midparent (ROMP) methods.

作者信息

Manolio Teri A, Barnes Kathleen C, Beaty Terri H, Levett Paul N, Naidu Raana P, Wilson Alexander F

机构信息

Division of Epidemiology and Clinical Applications, National Heart, Lung,and Blood Institute, 6701 Rockledge Drive, Rm. 8160, Bethesda, MD 20892-7934, USA.

出版信息

Hum Genet. 2003 Oct;113(5):437-46. doi: 10.1007/s00439-003-1005-6. Epub 2003 Aug 20.

Abstract

A genetic basis for asthma- and atopy-related quantitative traits, such as allergen-specific immunoglobulin E (IgE) levels, has been suggested by the observed familial aggregation of these traits in temperate climates. Less information is available for tropical climates, where different allergens may predominate. Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but heritability of B. tropicalis sensitivity and the impact of age, sex, and other environmental covariates on heritability have not been widely explored. Total and specific IgE levels were measured by immunochemiluminescent assay in 481 members of 29 Barbadian families (comprised of 340 parent-offspring trios or pairs) ascertained through two asthmatic siblings. Trait heritability was estimated using regression of offspring on mid-parent (ROMP) and pairwise correlation analysis of unadjusted IgE levels and on residual values after adjustment for covariates. Heritability of IgE levels to the major antigen of B. tropicalis (Blo t M) estimated by ROMP in 180 complete parent-offspring trios was 0.56. Heritability was consistently greater for male offspring than for female offspring. Similar sex-specific patterns were observed for specific IgE to Dermatophagoides pteronyssinus and total IgE levels and were relatively unaffected by adjustment for covariates. Pairwise correlational analyses of specific and total IgE levels showed similar results. Moderate heritability of Blo t M IgE levels was detected in these Barbadian families and was greater for sons than daughters. Adjustment for covariates had minimal impact. This suggests that future investigations of genetic determinants of IgE levels should include approaches that allow for potential sex differences in their expression.

摘要

在温带气候中,哮喘和特应性相关的数量性状(如过敏原特异性免疫球蛋白E(IgE)水平)呈现家族聚集现象,这提示了其遗传基础。而对于热带气候,相关信息较少,因为热带地区可能以不同的过敏原为主。在热带气候中,对热带螨类柏氏禽刺螨的敏感性与哮喘相关,但对柏氏禽刺螨敏感性的遗传力以及年龄、性别和其他环境协变量对遗传力的影响尚未得到广泛研究。通过两名哮喘患者同胞确定了29个巴巴多斯家庭的481名成员(包括340个亲子三人组或对子),采用免疫化学发光法测量其总IgE和特异性IgE水平。使用子代对中亲值的回归(ROMP)以及未调整的IgE水平和协变量调整后的残差值的成对相关分析来估计性状遗传力。在180个完整的亲子三人组中,通过ROMP估计的针对柏氏禽刺螨主要抗原(Blo t M)的IgE水平遗传力为0.56。男性子代的遗传力始终高于女性子代。对于针对尘螨的特异性IgE和总IgE水平,也观察到了类似的性别特异性模式,并且相对不受协变量调整的影响。特异性和总IgE水平的成对相关分析显示了类似的结果。在这些巴巴多斯家庭中检测到柏氏禽刺螨IgE水平具有中等遗传力,且儿子的遗传力大于女儿。协变量调整的影响最小。这表明未来对IgE水平遗传决定因素的研究应包括考虑其表达中潜在性别差异的方法。

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