Tanimura Kazuya, Aldrich Melinda C, Jaworski James, Xing Jinchuan, Okawa Satoshi, Chandra Divay, Nouraie Seyed M, Nyunoya Toru
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan.
Ann Hum Genet. 2025 May;89(2-3):89-95. doi: 10.1111/ahg.12587. Epub 2024 Dec 24.
The common genetic underpinnings of psoriasis and pulmonary comorbidities have yet to be explored.
In this cross-sectional study, we investigated the single-nucleotide polymorphisms (SNPs) associated with psoriasis and their relationship with pulmonary function using data from the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU).
Out of the 63 psoriasis-associated SNPs identified in previous genome-wide association studies within the European population, we successfully identified 53 SNPs, including proxy SNPs in UKBB database. Following adjustments using age and sex, 31 SNPs displayed statistically significant associations with psoriasis. Among these, 16 SNPs exhibited significant associations with forced expiratory volume in 1 s (FEV), 14 with forced vital capacity (FVC), and 5 with the FEV/FVC ratio in the UKBB. In the validation analysis using the BioVU database, 27 of the 31 psoriasis-associated SNPs were available for examination. Notably, the minor allele of SNP rs8016947 was confirmed to be significant, indicating a reduced risk for psoriasis and improved FEV. Similarly, the minor alleles of SNPs rs17716942 and rs8016947 were associated with a reduced risk of psoriasis and enhanced FVC. However, none of the 5 SNPs significantly associated with the FEV/FVC ratio in the UKBB displayed significance in the BioVU dataset.
This study has unveiled genetic variants that bridge the realms of psoriasis and lung function. The genes associated with these variants, including IFIH1, Grancalcin gene (GCA), and NFKB inhibitor alpha gene (NFKBIA), regulate innate immune responses, which suggests that immunodysregulation, a central element in psoriasis pathogenesis, may also impact lung function, alluding to a "skin-lung axis."
银屑病与肺部合并症的共同遗传基础尚未得到探索。
在这项横断面研究中，我们使用来自英国生物银行（UKBB）和范德比尔特大学医学中心生物银行（BioVU）的数据，研究了与银屑病相关的单核苷酸多态性（SNP）及其与肺功能的关系。
在先前欧洲人群全基因组关联研究中确定的63个与银屑病相关的SNP中，我们成功鉴定出53个SNP，包括UKBB数据库中的代理SNP。在按年龄和性别进行调整后，31个SNP与银屑病呈现出统计学上的显著关联。其中，16个SNP与UKBB中的1秒用力呼气量（FEV）显著相关，14个与用力肺活量（FVC）相关，5个与FEV/FVC比值相关。在使用BioVU数据库进行的验证分析中，31个与银屑病相关的SNP中有27个可供检测。值得注意的是，SNP rs8016947的次要等位基因被证实具有显著性，表明银屑病风险降低且FEV改善。同样，SNP rs17716942和rs8016947的次要等位基因与银屑病风险降低和FVC增强相关。然而，UKBB中与FEV/FVC比值显著相关的5个SNP在BioVU数据集中均未显示出显著性。
本研究揭示了连接银屑病和肺功能领域的基因变异。与这些变异相关的基因，包括IFIH1、颗粒钙蛋白基因（GCA）和NFKB抑制因子α基因（NFKBIA），调节先天性免疫反应，这表明免疫失调作为银屑病发病机制的核心要素，可能也会影响肺功能，暗示了“皮肤-肺轴”的存在。
