Guilloud-Bataille Michel, Bouzigon Emmanuelle, Annesi-Maesano Isabella, Bousquet Jean, Charpin Denis, Gormand Frédéric, Hochez Joëlle, Just Jocelyne, Lemainque Arnaud, Le Moual Nicole, Matran Régis, Neukirch Françoise, Oryszczyn Marie-Pierre, Paty Evelyne, Pin Isabelle, Vervloet Daniel, Kauffmann Francine, Lathrop Mark, Demenais Florence, Dizier Marie-Hélène
INSERM U535, Hôpital Paul Brousse, Bâtiment Leriche, B.P. 1000, 94817, Villejuif Cedex, France.
Hum Genet. 2008 Jan;122(6):605-14. doi: 10.1007/s00439-007-0439-7. Epub 2007 Oct 18.
Asthma, allergic rhinitis (AR) and atopic dermatitis also called eczema are allergic co-morbidites, which are likely to depend on pleiotropic genetic effects as well as on specific genetic factors. After a previous genome-wide linkage screen conducted for asthma and AR in a sample of 295 French EGEA families ascertained through asthmatic subjects, the aim here was to search for genetic factors involved in eczema and more particularly the ones shared by the three allergic diseases using the same EGEA data. In this sake, eczema and phenotypes of "allergic disease" accounting for the joint information on the presence/absence of the three diseases were examined by linkage analyses using the maximum likelihood binomial method. A fine mapping was carried out in regions detected for potential linkage, followed by association studies using the family-based association test (FBAT). Evidence for linkage to 11p14 region was shown for "allergic disease" and eczema. Linkage was also indicated between eczema and 5q13 and between "allergic disease" and both 5p15 and 17q21 regions. Fine mapping supported the evidence of linkage to 11p14 and FBAT analyses showed the association between "allergic disease" and a marker located at the linkage peak on 11p14. Further investigations in this region will allow identifying genetic factor(s) which could have pleiotropic effect in the three allergic diseases.
哮喘、变应性鼻炎(AR)和特应性皮炎(又称湿疹)均为过敏性共病,它们可能取决于多效性基因效应以及特定的遗传因素。此前,在通过哮喘患者确定的295个法国家庭样本中,针对哮喘和AR进行了全基因组连锁筛查,在此基础上本研究旨在利用相同的EGEA数据寻找与湿疹相关的遗传因素,尤其是这三种过敏性疾病共有的遗传因素。为此,采用最大似然二项式法,通过连锁分析对湿疹及涵盖这三种疾病存在与否联合信息的“过敏性疾病”表型进行了研究。在检测到潜在连锁的区域进行了精细定位,随后使用基于家系的关联检验(FBAT)进行关联研究。结果显示,“过敏性疾病”和湿疹与11p14区域存在连锁。湿疹与5q13之间以及“过敏性疾病”与5p15和17q21区域之间也显示出连锁。精细定位支持了与11p14连锁的证据,FBAT分析显示“过敏性疾病”与位于11p14连锁峰处的一个标记存在关联。对该区域的进一步研究将有助于识别可能在这三种过敏性疾病中具有多效性作用的遗传因素。