Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations
Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations
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DOI：
10.1111/j.1365-2133.2011.10331.x
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发表时间：
2011-07-01
影响因子：
10.3
通讯作者：
Lane, E. B.
中科院分区：
文献类型：
--
作者：
Chen, H.;Common, J. E. A.;Lane, E. B.
聚丝蛋白基因（FLG）的零突变可引起寻常性鱼鳞病（IV）并易患特应性皮炎（AD）。欧洲和日本的队列研究报道了FLG突变携带频率在14%至56%之间，但在中国IV和AD患者中，流行的欧洲FLG突变很少或不存在。目的进一步研究中国患者FLG-null突变谱，并与其他人群进行比较。我们对92名患有IV和/或中重度AD的新加坡华人进行了全面的FLG遗传分析。然后在425名AD患者和440名正常对照中筛选所有检测到的FLG突变。结果共鉴定出22个FLG-null突变，其中14个为新突变；在病例和对照组中检测到的17个突变的FLG基因型与AD有很强的相关性[Fisher精确检验；P = 5.3 × 10(-9)；优势比（OR） 3.3]，手掌超线性(Fisher精确检验；P = 9.0 × 10(-15)；OR 5.8)、毛角化病（Fisher精确检验，P = 0.001; OR 4.7）以及AD严重程度的增加（置换检验，P = 0.0063）。结论：本研究强调了在亚洲缓慢出现的FLG-null突变的更广泛的遗传格局。
Background Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD.Objectives To investigate further the spectrum of FLG-null mutations in Chinese patients and to compare it with that in other populations.Methods We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate-to-severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls.Results In total, 22 FLG-null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher's exact test; P = 5.3 x 10(-9); odds ratio (OR) 3.3], palmar hyperlinearity (Fisher's exact test; P = 9.0 x 10(-15); OR 5.8), keratosis pilaris (Fisher's exact test; P = 0.001; OR 4.7) and with increased severity of AD (permutation test; P = 0.0063).Conclusions This study emphasizes the wider genetic landscape of FLG-null mutations in Asia that is slowly emerging.