Department of Dermatology, Xinhua Hospital, Shanghai, China.
Allergy. 2011 Mar;66(3):420-7. doi: 10.1111/j.1398-9995.2010.02493.x. Epub 2010 Oct 8.
Recently, loss-of-function mutations in the filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and also predisposing factors for atopic dermatitis (AD) and AD-associated phenotypes. Until now, over thirty mutations in FLG have been identified in patients with IV and AD, but the FLG mutation spectrum is not clear for Chinese Han patients with AD. This study aimed to investigate the role of FLG mutations in AD and AD-associated phenotypes in a Chinese population.
We carried out a comprehensive sequencing of the entire FLG coding region in 261 Han AD patients.
In our research, we identified ten novel mutations (R826X, 3222del4, R1140X, 4271delAA, Q1790X, 5757del4, 6834del5, 6950del8, S2706X and K4671X) and eight reported mutations (441delA, R501X, 3321delA, R1474X, Q2417X, E2422X, 7945delA and R4306X) in FLG. FLG mutations were present in 31.4% of our AD patients. Mutations 3321delA and K4671X, with a frequency of 14.6% and 9.2%, respectively, were two of the most common mutations in this AD cohort. FLG null alleles (compound genotypes) were significantly associated with AD (P < 0.001) and AD associated with food sensitization (P = 0.012). However, we did not observe a positive association between FLG mutations and other AD-associated phenotypes, including asthma, allergic rhinitis and elevated total serum IgE level.
Our study increases the total number of reported FLG mutations. Moreover, we further confirm that FLG mutations are strong predisposing factors for AD in Han Chinese.
最近,丝聚蛋白基因(FLG)的功能丧失性突变被确定为寻常型鱼鳞病(IV)的病因,也是特应性皮炎(AD)和 AD 相关表型的易感因素。到目前为止,已有三十多种 FLG 突变在 IV 和 AD 患者中被发现,但中国汉族 AD 患者的 FLG 突变谱尚不清楚。本研究旨在探讨 FLG 突变在中国人群 AD 和 AD 相关表型中的作用。
我们对 261 例汉族 AD 患者进行了 FLG 整个编码区的全面测序。
在我们的研究中,我们鉴定了十个新突变(R826X、3222del4、R1140X、4271delAA、Q1790X、5757del4、6834del5、6950del8、S2706X 和 K4671X)和八个已报道的突变(441delA、R501X、3321delA、R1474X、Q2417X、E2422X、7945delA 和 R4306X)在 FLG 中。FLG 突变在我们的 AD 患者中占 31.4%。突变 3321delA 和 K4671X 的频率分别为 14.6%和 9.2%,是该 AD 队列中最常见的两种突变。FLG 无功能等位基因(复合基因型)与 AD 显著相关(P<0.001),与食物过敏相关的 AD(P=0.012)。然而,我们没有观察到 FLG 突变与其他 AD 相关表型(包括哮喘、过敏性鼻炎和总血清 IgE 水平升高)之间存在阳性关联。
本研究增加了报告的 FLG 突变总数。此外,我们进一步证实 FLG 突变是汉族人群 AD 的强易感因素。