Haagerup A, Bjerke T, Schiøtz P O, Dahl R, Binderup H G, Kruse T A
Institute of Human Genetics, Bartholin Building, Aarhus University, DK-8000 Aarhus C, Denmark.
Allergy. 2001 Aug;56(8):775-9. doi: 10.1034/j.1398-9995.2001.056008775.x.
Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type I allergy to the IL4R variations I50V and Q576R, and investigated chromosome 16 for atopy candidate regions in general.
We identified 100 Danish allergy sib-pair families. Five conservative phenotypes for type I allergy were defined and evaluated. The IL4R variations were genotyped in trios and evaluated by the transmission disequilibrium test (TDT). Multipoint linkage analysis and exclusion mapping were conducted with sib-pairs analyzed for 17 microsatellite markers.
No evidence for association or linkage to the IL4R polymorphisms was found (P values: 0.12-0.90). Linkage analysis did not support linkage of any of the phenotypes to chromosome 16. Major parts of chromosome 16 were excluded as candidate regions harboring oligogenes for type I allergy.
We found chromosome 16 unlikely to harbor strong candidate genes for type I allergy. The role of the IL4Ralpha gene in the inheritance of atopy was insignificant in the Danish population. The use of conservative allergy phenotypes in the search for genes predisposing to atopic disease was discussed.
近年来已提出几种特应性的易感基因。很少有基因像16号染色体上的白细胞介素-4受体α（IL4Rα）基因那样得到深入研究。结果仍存在争议。因此，在一项严谨的设计中，我们检测了I型过敏与IL4R变异I50V和Q576R的关联性，并总体上研究了16号染色体上的特应性候选区域。
我们确定了100个丹麦过敏同胞对家庭。定义并评估了I型过敏的五种保守表型。对三联体进行IL4R变异的基因分型，并通过传递不平衡检验（TDT）进行评估。对同胞对进行17个微卫星标记的分析，进行多点连锁分析和排除定位。
未发现与IL4R多态性相关或连锁的证据（P值：0.12 - 0.90）。连锁分析不支持任何表型与16号染色体连锁。16号染色体的主要部分被排除为含有I型过敏寡基因的候选区域。
我们发现16号染色体不太可能含有I型过敏的强候选基因。在丹麦人群中，IL4Rα基因在特应性遗传中的作用不显著。讨论了在寻找特应性疾病易感基因时使用保守过敏表型的问题。
