Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.
Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.
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在一项家庭关联研究中，常见的 FLG 突变 K4671X 与汉族人的特应性皮炎无关。
DOI：
10.1371/journal.pone.0049158
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yao Z
中科院分区：
文献类型：
--
作者：
Cheng R;Li M;Zhang H;Guo Y;Chen X;Tao J;Jiang A;Gan J;Qi H;Yu H;Liao W;Yao Z
聚丝蛋白基因（FLG）突变已被确定为寻常性鱼鳞病（IV）的原因和特应性皮炎（AD）的主要易感因素。AD、IV和FLG突变之间的关系尚未明确。突变3321delA和K4671X是中国患者中最常见的两种突变，在病例对照研究中均与AD有统计学相关性。招募了100个家庭三组（共有300个成员，其中一个受影响的AD先证者和父母双方）并筛选了三个聚丝蛋白无效突变（3222del4, 3321delA和K4671X）。由两位经验丰富的皮肤科医生对受试者的AD和IV表现进行评估并详细记录。使用病例对照和基于家庭的关联测试来评估常见突变与AD的关系。采用实时荧光定量RT-PCR和免疫组织化学方法检测3例K4671X杂合子和正常人皮肤中聚丝蛋白的表达。100例AD先证中，22例为常见FLG突变携带者，其中仅有2例来自40例非iv家族三联体（5.00%），与健康对照组（3.99%,P < 0.05）一致。AD与3321delA （P<0.001，优势比12.28,95%可信区间3.35 ~ 44.98）、K4671X （P = 0.002，优势比4.53,95%可信区间1.77 ~ 11.60）具有显著的统计学相关性。基于家族的方法发现，K4671X与AD的传代不平衡（T:U = 10∶8,P = 0.815），但K4671X与AD的传代不平衡（T:U = 12∶1,P = 0.003）。此外，与正常对照相比，K4671Xheter患者表皮中聚丝蛋白mRNA和蛋白水平的表达均未降低。来自非iv家族的AD患者携带FLG突变的可能性较低。本家族样本证实了突变3321delA对汉族AD的易感性。K4671X不是致病突变。
Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies. A group of 100 family trios (a total of 300 members with one affected AD proband and both parents) were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects’ manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry. Of 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of the healthy control group (3.99%, P>0.05). Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35–44.98) as well as K4671X (P = 0.002, odds ratio 4.53, 95% confidence interval 1.77–11.60). The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U = 12∶1, P = 0.003) but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U = 10∶8, P = 0.815). Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671Xheter was not reduced. AD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a pathogenic mutation.
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