Filaggrin Gene Mutation c.3321delA Is Associated with Various Clinical Features of Atopic Dermatitis in the Chinese Han Population

Li, Meng; Wang, Li; Tang, Huayang; Tang, Xianfa; Jiang, Xiaoyun; Zhao, Jing; Gao, Jing; Li, Bing; Fu, Xuhui; Chen, Yan; Yao, Weiyi; Zhan, Wenjing; Wu, Bo; Duan, Dawei; Shen, Changbing; Cheng, Hui; Zuo, Xianbo; Yang, Sen; Sun, Liangdan; Zhang, Xuejun

doi:10.1371/journal.pone.0098235

Cited by 29 publications

(29 citation statements)

References 33 publications

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“…2b). This is consistent with a recent report on 1080 Chinese AD cases which found no association between pan-Asian c.3321delA and asthma (9). Thus, considering that filaggrin is not expressed in the upper airway, the role of FLG mutation(s) as an initiator of allergic march should be critically re-evaluated after further accumulation of experimental/epidemiological data.…”

Section: Resultssupporting

confidence: 90%

FLG mutations in the East Asian atopic dermatitis patients: genetic and clinical implication

Park

et al. 2016

Experimental Dermatology

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BackgroundSince the report on the association between FLG mutations and atopic dermatitis (AD) (1), genetic diversity of FLG mutations has been intensively investigated across ethnicities. However, except for well-established racial difference between European and Asian (2), detailed analysis of the genetic diversity and clinical implications of FLG mutations for East Asian ancestry was not performed yet. Questions addressedThe purpose of this study was, first, to overview genetic landscape of FLG mutations across East Asia and to analyse geographic distribution from genealogic point of view, especially prehistoric human migration in East Asia. Second, we investigated the association of FLG mutations with clinical features of AD to evaluate the clinical significance of FLG mutations. Experimental designWe collected data reporting FLG mutations among East Asian populations, including recently completed full sequencing of FLG for Koreans in our laboratory. In total, 1384 AD cases and 1031 normal controls were identified for three East Asian populations at six locations: Chinese Han/Singapore, Chinese Han/Shanghai, Chinese Han/Shanxi, Korean, Japanese/Kyushu and Japanese/ mainland (Table S1). From mutational diversity, genetic distances were calculated and visualized as phylogenetic trees. Ancestryrelated population structures were inferred by clustering software, STRUCTURE (3). To assess the significance of FLG mutations as clinical biomarkers, statistical tests were performed, and Review Manager (RevMan) (4) was employed for population pooled analysis and graphical presentation of results. Detailed information on 'Materials and Methods' can be found in the (Data S1). ResultsThe geographic distribution of FLG mutations is summarized in Fig. 1a, with several notable patterns. First, c.3321delA was re-confirmed as a pan-Asian mutation, found in all populations. Meanwhile, some mutations showed south-to-north (or north-to-south) distribution gradient: p.K4022X, the most prevalent FLG mutation in northern China and Korea, declined in frequency moving southward; in contrast, c.6950del8 (p.Q2417X, p.E2422X, etc.) showed the reverse. Finally, several mutations (p.S2554X/p.S2889X/p.S329 6X/Q1701X) were Japanese-specific and not found elsewhere.Phylogenetic tree clearly showed separation of Asian from European (Irish) and branching of Japanese, Korean, northern/southern Chinese Han successively (Fig. 1b, far-left). STRUCTURE analysis revealed that at least three ancestries contributed to the current genetic make-up of East Asian AD patients: south-to-north, northto-south and Japanese-specific ancestries (Fig. 1b,. These three ancestries were replicated in other genetic data, such as autosomal (Fig. 1b Table S1 for details). Hypothetical human migration routes are depicted by blue arrows. data sets (Fig. 1b, far-right) (6). For the presence of Japanese-specific FLG mutations, so-called dual origin of Japanese could provide possible explanations. Historic/archaeological data suggested two ancestries for current Japanese: Jom...

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Section: Resultssupporting

confidence: 90%

FLG mutations in the East Asian atopic dermatitis patients: genetic and clinical implication

Park

et al. 2016

Experimental Dermatology

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“…There are ethnic differences in the association of FLG mutations with AD; in Asian populations, filaggrin P478S and C3321delA – variants not commonly found in European populations – are associated with increased risk of AD, the atopic march and recurrent skin infections . By contrast, in African American children, loss‐of‐function mutations in FLG2 , but not FLG , are associated with increased AD risk .…”

Section: Skin Barrier Dysfunctionmentioning

confidence: 99%

Atopic dermatitis: the skin barrier and beyond

et al. 2018

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Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high-risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma.

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“…Association between filaggrin mutation and AD has been confirmed by several studies . To date, besides the two most common mutations in the European population (R501X and 2282del4), more than 60 mutations have been reported, all leading to loss‐of‐filaggrin expression . There are unique spectrums of filaggrin mutation in different ancestral population, and distinct FLG mutation landscapes have been reported in Asia and Europe; furthermore, prevalence of specific mutations of European (R501X,2282del4) in Asian population is low .…”

Section: Introductionmentioning

confidence: 88%

“…13,22,23,32,33 To date, besides the two most common mutations in the European population (R501X and 2282del4), more than 60 mutations have been reported, all leading to loss-of-filaggrin expression. 22,34,35 There are unique spectrums of filaggrin mutation in different ancestral population, and distinct FLG mutation landscapes have been reported in Asia and Europe; 1,22,36 furthermore, prevalence of specific mutations of European (R501X,2282del4) in Asian population is low. 36 The mutation spectrum varies in Asian populations, and few filaggrin mutations are overlapping among some Asian populations.…”

Section: Introductionmentioning

confidence: 99%

Filaggrin gene polymorphisms in Iranian ichthyosis vulgaris and atopic dermatitis patients

et al. 2018

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Background Filaggrin is a key structural epidermal protein in terminal differentiation and formation of skin barrier. The important role of filaggrin and its effects in various cutaneous and noncutaneous disorders initiated a cascade of considerable research in recent years. Loss‐of‐function mutations in FLG, the human gene encoding profilaggrin/filaggrin, is the cause of the common skin condition ichthyosis vulgaris (IV) and major genetic predisposing factor for atopic dermatitis (AD). Several null mutations in the FLG gene that lead to a decrease or absence of filaggrin in skin and predispose these conditions have been described. Objective The aim of this study was to investigative genetic polymorphism of FLG in Iranian patients with IV and AD. Methods In the current study, we carried out full sequencing of the entire FLG coding region in 30 IV patients and 30 AD patients, and also 60 healthy controls. Results In our research, we identified 43 variants reported previously and two novel variants. Conclusion In our study, in the AD and IV patients, loss‐of‐function FLG mutation was not found. This means that another mechanism other than FLG nonsense mutation is involved in the pathogenesis of these patients.

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Filaggrin Gene Mutation c.3321delA Is Associated with Various Clinical Features of Atopic Dermatitis in the Chinese Han Population

Cited by 29 publications

References 33 publications

FLG mutations in the East Asian atopic dermatitis patients: genetic and clinical implication

FLG mutations in the East Asian atopic dermatitis patients: genetic and clinical implication

Atopic dermatitis: the skin barrier and beyond

Filaggrin gene polymorphisms in Iranian ichthyosis vulgaris and atopic dermatitis patients

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