Center for Rare Systemic Auto-immune Diseases, Department of Rheumatology, Centre Hospitalier du Mans, 194 avenue Rubillard, 72000 Le Mans, France.
Ann Rheum Dis. 2011 Apr;70(4):653-9. doi: 10.1136/ard.2010.142760. Epub 2010 Dec 3.
In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear.
A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis.
The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10(-5)). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005).
RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.
在囊性纤维化中，CFTR 基因突变导致弥漫性支气管扩张（DB）。DB 还与其他疾病相关，包括类风湿关节炎（RA），其中遗传因素在 DB 的易感性中的作用尚不清楚。
进行了一项基于家族的关联研究，以确定 RA 相关 DB 患者中 CFTR 基因突变的频率是否更高，并通过评估其在家族内与 DB 的共分离来确定该变体与疾病之间是否存在因果关系。如果先证者的一级亲属患有 RA 和/或 DB，则将具有 RA-DB 的家系纳入研究。对照组包括因伴侣患有囊性纤维化而要求进行遗传咨询的健康受试者。
与未受影响的亲属（每次比较 p<0.005）和无关的健康对照组（每次比较 p<0.001）相比，具有 RA-DB 或仅 DB 的家庭成员中 CFTR 基因突变的频率更高，但具有仅 RA 的家庭成员中 CFTR 基因突变的频率没有更高。具有 RA-DB 的家庭成员中 CFTR 基因突变的频率高于仅具有 RA 的家庭成员（OR 5.30，95%CI 2.48 至 11.33；p<5×10(-5)）。它们在家系中与 RA-DB 共分离（sib-TDT=10.82，p=0.005）。
RA-DB 应添加到 CFTR 基因突变具有致病性的表型列表中。CFTR 突变是第一个与 RA 的关节外特征相关的遗传缺陷。RA 患者的 CFTR 突变似乎是相关 DB 风险的重要标志物，DB 与预后较差有关。
