Mutations analysis in filaggrin gene in northern China patients with atopic dermatitis
Mutations analysis in filaggrin gene in northern China patients with atopic dermatitis
复制标题
中国北方特应性皮炎患者丝聚蛋白基因突变分析
DOI：
10.1111/j.1468-3083.2011.04435.x
复制
发表时间：
2013-02-01
影响因子：
9.2
通讯作者：
Yao, Z.
中科院分区：
文献类型：
--
作者：
Li, M.;Liu, Q.;Yao, Z.
最近，我们报道了中国南方地区特应性皮炎的聚丝蛋白突变（FLG）。然而，目前关于中国北方AD患者FLG突变的详细报道还很少。目的建立中国北方AD患者FLG基因突变谱。方法收集符合Hanifin和Rajka诊断标准的AD患者339例。对这些患者的整个FLG编码区进行了全面的测序。所有检测到的FLG零突变在301名正常对照中进行筛选。结果共鉴定出7个AD新突变（478insA、Q1070X、4026delT、Q1712X、Q2397X、7145del4和8001del4）和11个AD已报道突变（3222del4、3321delA、4271delAA、S1515X、Q1790X、5757del4、6834del5、Q2417X、E2422X、7945delA和K4671X）。突变3321delA和K4671X是AD中最常见的两个突变。26.0%的AD患者存在FLG零突变。AD患者FLG零等位基因（复合基因型）显著高于对照组（P < 0.001）。所有FLG变异的复合基因型与IV （P < 0.001）和掌部超线性（P < 0.001）显著相关。常见突变K4671X与ad共存的变应性鼻炎显著相关（P = 0.005）。结论本研究增加了FLG突变的总数。我们清楚地证明了FLG功能缺失突变与中国北方AD显著相关。中国人群的FLG零突变不仅与欧洲人群不同，而且与中国大陆以外的亚洲亚人群也不同。
Background Recently, we have reported filaggrin mutations (FLG) of atopic dermatitis in southern China. However, there have been few detailed reports of FLG mutations of patients with AD in northern China by now. Objectives The present aim was to establish the mutation spectrum of FLG gene in AD patients in northern China.Methods A total of 339 cases met Hanifin and Rajka diagnostic criteria of AD were recruited. A comprehensive sequencing of the entire FLG coding region in these patients was conducted. All detected FLG null mutations were screened in a cohort of 301 normal controls.Results Seven novel mutations (478insA, Q1070X, 4026delT, Q1712X, Q2397X, 7145del4 and 8001del4) and eleven reported mutations (3222del4, 3321delA, 4271delAA, S1515X, Q1790X, 5757del4, 6834del5, Q2417X, E2422X, 7945delA and K4671X) in AD were identified. Mutations 3321delA and K4671X were two of the most common mutations in AD. FLG null mutations were present in 26.0% of AD patients. FLG null alleles (compound genotypes) were significantly higher in AD (P < 0.001) than in the controls. The compound genotypes for all FLG variants were significantly associated with IV (P < 0.001) and palmar hyperlinearity (P < 0.001). The common mutation, K4671X, was significantly associated with AD-coexistent allergic rhinitis (P = 0.005).Conclusions Our study increases the total number of FLG mutations. We clearly demonstrated that FLG loss-of-function mutations were significantly associated with AD in northern China. The FLG null mutations in the Chinese population differed not only from that in the European population but also from that in sub-populations of Asians outside of the Chinese mainland.