Fulton Rachel L, Margolis David J, Sockler Patrick G, Mitra Nandita, Wong Xuan Fei Colin Cornelius, Common John E
Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Exp Dermatol. 2022 Feb;31(2):233-236. doi: 10.1111/exd.14449. Epub 2021 Aug 21.
Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a multifactorial pathophysiology. The filaggrin gene (FLG) has particularly been implicated given loss of function (LoF) mutations in this gene lead to skin barrier dysfunction and such mutations can increase a patient's likelihood of developing AD. FLG has intragenic copy number variation (CNV), which impacts the total amount of filaggrin produced. Previous research reported a dose-dependent effect such that as amount of FLG increases, risk of AD decreases. To gain a better understanding, we evaluated FLG CNV in a large case-control study of Whites and Blacks with and without AD. The goal of our study was to determine whether FLG CNV has a dose-dependent effect on the risk of developing AD and to determine whether FLG CNV varies by race. The frequencies and odds ratios comparing a given CNV by race or race within those with AD did not significantly vary. It had been thought that FLG CNV might vary by race and represent an important association with AD in Black AD subjects. However, our work suggests that while there are racial differences with respect to CNV, these differences do not appear to explain AD risk.
特应性皮炎（AD）是一种具有多因素病理生理学的慢性炎症性皮肤病。鉴于丝聚合蛋白基因（FLG）的功能丧失（LoF）突变会导致皮肤屏障功能障碍，且此类突变会增加患者患AD的可能性，因此该基因尤其受到关注。FLG存在基因内拷贝数变异（CNV），这会影响所产生的丝聚合蛋白的总量。先前的研究报道了一种剂量依赖性效应，即随着FLG数量的增加，AD风险降低。为了更好地理解，我们在一项针对患有和未患有AD的白人和黑人的大型病例对照研究中评估了FLG CNV。我们研究的目的是确定FLG CNV是否对患AD的风险有剂量依赖性影响，以及FLG CNV是否因种族而异。按种族或AD患者中的种族比较给定CNV的频率和优势比没有显著差异。人们曾认为FLG CNV可能因种族而异，并在黑人AD患者中代表与AD的重要关联。然而，我们的研究表明，虽然在CNV方面存在种族差异，但这些差异似乎无法解释AD风险。
