Copy-number variation of the filaggrin gene in Korean patients with atopic dermatitis: what really matters, ‘number’ or ‘variation’?

Li, K.; Seok, Joon; Park, K. Y.; Yoon, Yoosik; Kim, Kyu-Han; Seo, Sang Woo

doi:10.1111/bjd.14287

Cited by 15 publications

(14 citation statements)

References 10 publications

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“…When we compared the AD and HC groups, we found that 10 different variations (the 3′ untranslated region AACC insertion 5874 of KLK7 , along with FLG 3321delA, SPINK5‐ 1156, SPINK5‐ 2475, DEFB1 rs5743399, KDR rs2305948, IL5RA rs334809, IL9 rs31563, IL12RB1 rs393548 and IL12RB1 rs436857), were statistically significant. We also assessed the heterozygous mutant of FLG pK4022X, which was significant in a previous Korean study, and the homozygous mutant of SPINK5‐ 1188, which shows a higher tendency in patients with AD. Thus, we eventually compared 12 SNPs according to overlap of gene variations between the HC, mild AD and moderate/severe AD groups.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, there have many reports involving genetic and epigenetic studies of AD, especially skin barrier function and innate/adaptive immune responses . In the current study, we aimed to determine the known variations in the genes FLG , SPINK5 , KLK7 , DEFB , TNF α, KDR , FCER1A , IL4 , IL5 , IL5RA , 8 IL9 , IL10 , IL12, IL12R , IL13 , and IL18 , using data reported for East Asian patients with AD.…”

Section: Discussionmentioning

confidence: 99%

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Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Hy²,

Murai

et al. 2018

Clin Exp Dermatol

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Hy²,

Murai

et al. 2018

Clin Exp Dermatol

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“…Previous studies documented that the copy number of subexonic filaggrin repeats can vary from 10 to 12 copies in human populations and dose-dependent correlation between reduced atopic dermatitis risk and the copy number of filaggrin repeats in Irish (Brown et al 2012), Korean (Li et al 2016) and African American populations (Quiggle et al 2015). Since the current pipeline for constructing the 1-kGP dataset was not able to detect subexonic FLG copy number variants (CNVs), we used long-range polymerase chain reaction to genotype these variants in 126 samples from different ancestral backgrounds that are included in 1-kGP dataset (supplementary fig.…”

Section: Resultsmentioning

confidence: 99%

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Eaaswarkhanth

Flanagan

et al. 2016

Genome Biol Evol

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Human skin has evolved rapidly, leaving evolutionary signatures in the genome. The filaggrin (FLG) gene is widely studied for its skin-barrier function in humans. The extensive genetic variation in this gene, especially common loss-of-function (LoF) mutations, has been established as primary risk factors for atopic dermatitis. To investigate the evolution of this gene, we analyzed 2,504 human genomes and genotyped the copy number variation of filaggrin repeats within FLG in 126 individuals from diverse ancestral backgrounds. We were unable to replicate a recent study claiming that LoF of FLG is adaptive in northern latitudes with lower ultraviolet light exposure. Instead, we present multiple lines of evidence suggesting that FLG genetic variation, including LoF variants, have little or no effect on fitness in modern humans. Haplotype-level scrutinization of the locus revealed signatures of a recent selective sweep in Asia, which increased the allele frequency of a haplotype group (Huxian haplogroup) in Asian populations. Functionally, we found that the Huxian haplogroup carries dozens of functional variants in FLG and hornerin (HRNR) genes, including those that are associated with atopic dermatitis susceptibility, HRNR expression levels and microbiome diversity on the skin. Our results suggest that the target of the adaptive sweep is HRNR gene function, and the functional FLG variants that involve susceptibility to atopic dermatitis, seem to hitchhike the selective sweep on HRNR. Our study presents a novel case of a locus that harbors clinically relevant common genetic variation with complex evolutionary trajectories.

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“…Therefore, FLG deficiency alone seems insufficient to explain epidermal barrier dysfunction in these patients. In addition to various mutations, copy number variation within FLG also increases the risk of AD [20,21], and the levels of filaggrin degradation products in the stratum corneum are correlated with the FLG genotype or copy number and AD severity [21,22]. Hornerin and FLG2 are fused S-100 proteins that are functionally related to FLG.…”

Section: Geneticsmentioning

confidence: 99%

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

Kim

Cho

et al. 2016

IJMS

110

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Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology.

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Copy-number variation of the filaggrin gene in Korean patients with atopic dermatitis: what really matters, ‘number’ or ‘variation’?

Cited by 15 publications

References 10 publications

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay

Atopic Dermatitis Susceptibility Variants in FilaggrinHitchhikeHornerin Selective Sweep

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

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