To the Editors:
我们感兴趣地阅读了朱的文章等。1描述了两个单核苷酸多态性(SNP; RS231775和RS3087243)在CTLA4基因和慢性支气管炎中的关联。这两种多态性都可能是自身免疫性的危险因素2,通常被称为A49G和CT60。正如作者在讨论中简要提到的那样,最近人们对自身免疫性在慢性阻塞性肺疾病中的可能作用引起了人们的兴趣,因此与其他自身免疫性疾病共享遗传敏感性将支持这一假设。尽管作者以两个独立的队列报告了他们的关联,但对该基因座的重要性的普遍接受将需要在其他COPD人群中进行进一步验证。我们想通过在α中报告rs231775的关联来增加其结果的支持1-antitrypsin deficient (α1-ATD) cohort, which also tended to associate with the same feature in the 1958 birth cohort.
如前所述3,并使用Taqman®(Applied Biosystems,Applied Biosystems,美国加利福尼亚州,美国加利福尼亚州)进行基因分型和RS3087243。1 s的慢性支气管炎和强迫呼气量的关联(FEV1分别使用逻辑和线性回归来寻求),以调整年龄,性别和烟熏的年龄。该组的特征如表1所示⇓。基因分型成功率超过90%,两个SNP都处于耐寒与韦恩伯格的平衡状态。与FEV有关的数据1协会与单核苷酸多态性和周围的再保险gion were obtained from published online data of the 1958 birth cohort4。
The G allele of rs231775 associated with lower FEV1(B = -4.22; p = 0.04), but not with chronic bronchitis. No associations were seen with rs3087243. In data deposited by J. Todd (University of Cambridge, Cambridge, UK) and published online by the 1958 birth cohort4,,,,rs231775 tended to be associated with FEV1,,,,such that those with the G allele had lower FEV1与AA纯合子相比(b = -0.053,95%CI -0.101--0.005; p = 0.09)。从RS231775的基因的5'端仅4 kb的SNP显着相关(b = 0.098,95%CI 0.032 -0.163; p = 0.01)。
It is recognised that subjects with α1-ATD表现出与通常COPD中的COPD表型相似的COPD表型的遗传关联5,以使任何个体多态性的效果都添加到α上1-ATD. In this cohort, association with chronic bronchitis was not seen, perhaps because the study was underpowered. Although there was some linkage disequilibrium (LD) between rs231775 and rs3087243 (r2 = 0.59), slightly higher than that observed by Zhu等。1in their cohorts, no associations with the latter SNP were seen. The degree of LD between the SNPs may account for their shared susceptibility to chronic bronchitis in the original publication by Zhu等。1,由于我们的数据集中的功率较低,因此无法检测到。在自身免疫性疾病中CTLA4并不完全集中在RS231775和RS3087243上2,这可能解释了这里与后者SNP缺乏关联,以及1958年出生队列中RS231775上游的协会。这表明更详细的映射CTLA4polymorphisms in COPD may be able to detect the true associated variant.
我们的工作也支持CTLA4in COPD, albeit with a different related phenotype. The suggestive data from the 1958 birth cohort goes some way to corroborating this. Further study of autoimmunity associated loci in COPD may help to establish whether this is an important aspect of pathogenesis.
利益声明
None declared.
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