Hizawa N, Freidhoff L R, Chiu Y F, Ehrlich E, Luehr C A, Anderson J L, Duffy D L, Dunston G M, Weber J L, Huang S K, Barnes K C, Marsh D G, Beaty T H
Johns Hopkins Asthma & Allergy Center, School of Medicine, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 1998 Sep;102(3):436-42. doi: 10.1016/s0091-6749(98)70132-0.
Dermatophagoides pteronyssinus (Der p) is one of the most frequently implicated allergens in atopic diseases. Although HLA could play an important role in the development of the IgE response to the Der p allergens, genetic regulation by non-HLA genes influences certain HLA-associated IgE responses to complex allergens.
To clarify genetic control for the expression of Der p-specific IgE responsiveness, we conducted a genome-wide search for genes influencing Der p-specific IgE antibody levels by using 45 Caucasian and 53 African American families ascertained as part of the Collaborative Study on the Genetics of Asthma (CSGA).
Specific IgE antibody levels to the Der p crude allergen and to the purified allergens Der p 1 and Der p 2 were measured. Multipoint, nonparametric linkage analysis of 370 polymorphic markers was performed with the GENEHUNTER program.
The best evidence of genes controlling specific IgE response to Der p was obtained in 2 novel regions: chromosomes 2q21-q23 (P = .0033 for Caucasian subjects) and 8p23-p21 (P = .0011 for African American subjects). Three regions previously proposed as candidate regions for atopy, total IgE, or asthma also showed evidence for linkage to Der p-specific IgE responsiveness: 6p21 (P = .0064) and 13q32-q34 (P = 0.0064) in Caucasian subjects and 5q23-q33 (P = 0.0071) in African American subjects.
No single locus generated overwhelming evidence for linkage in terms of established criteria and guidelines for a genome-wide screening, which supports previous assertions of a heterogeneous etiology for Der p-specific IgE responsiveness. Two novel regions, 2q21-q23 and 8p23-p21, that were identified in this study merit additional study.
屋尘螨（Der p）是特应性疾病中最常见的致敏原之一。尽管人类白细胞抗原（HLA）在对Der p致敏原的IgE反应发展中可能起重要作用，但非HLA基因的遗传调控会影响某些与HLA相关的对复合致敏原的IgE反应。
为阐明Der p特异性IgE反应性表达的遗传控制，我们通过使用作为哮喘遗传学协作研究（CSGA）一部分确定的45个白种人家族和53个非裔美国家族，对影响Der p特异性IgE抗体水平的基因进行了全基因组搜索。
测定了针对Der p粗制致敏原以及纯化致敏原Der p 1和Der p 2的特异性IgE抗体水平。使用GENEHUNTER程序对370个多态性标记进行多点非参数连锁分析。
在2个新区域获得了控制对Der p特异性IgE反应的基因的最佳证据：2号染色体q21-q23（白种人受试者P = 0.0033）和8号染色体p23-p21（非裔美国家族受试者P = 0.0011）。先前提出的作为特应性、总IgE或哮喘候选区域的3个区域也显示出与Der p特异性IgE反应性连锁的证据：白种人受试者中的6号染色体p21（P = 0.0064）和13号染色体q32-q34（P = 0.0064），以及非裔美国家族受试者中的5号染色体q23-q33（P = 0.0071）。
就全基因组筛选的既定标准和指南而言，没有单个基因座产生压倒性的连锁证据，这支持了先前关于Der p特异性IgE反应性病因异质性的论断。本研究中确定的2个新区域2q21-q23和8p23-p21值得进一步研究。
