Filaggrin null mutations and childhood atopic eczema: A population-based case-control study

Brown, Sara J.; Relton, Caroline L; Liao, Hong; Zhao, Yiwei; Sandilands, Aileen; Wilson, I. J.; Burn, John; Reynolds, Nick J.; McLean, W.H. Irwin; Cordell, Heather J.

doi:10.1016/j.jaci.2008.01.013

Cited by 142 publications

(148 citation statements)

References 38 publications

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“…Subsequently an impressive series of replication studies [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] confirmed that these polymorphisms confer an exceptionally strong risk for eczema and subsequent allergen sensitization and that FLG is one of the strongest known genes for complex diseases in general [22][23][24][25] .…”

Section: Resultsmentioning

confidence: 99%

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Weidinger

Baurecht

Wagenpfeil

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Resultsmentioning

confidence: 99%

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Weidinger

Baurecht

Wagenpfeil

et al. 2008

Journal of Allergy and Clinical Immunology

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“…In milder, community-based cases of eczema (i.e. mild eczema presenting to general practitioners and not requiring specialist dermatologist referral), filaggrin is also an important risk factor (Brown et al, 2008); however, the association is much stronger in case-control association studies of individuals with moderate-to-severe eczema presenting to secondary-care clinics ; again, this reflects the more severe disease trajectory that is predicted by filaggrin deficiency.…”

Section: Eczemamentioning

confidence: 99%

Filaggrin in the frontline: role in skin barrier function and disease

Sandilands

Sutherland

Irvine

et al. 2009

Journal of Cell Science

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685

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Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin and filaggrin, have been identified as the cause of the common skin condition ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations, which are carried by up to 10% of people, also represent a strong genetic predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the major component of the keratohyalin granules within epidermal granular cells. During epidermal terminal differentiation, the ~400 kDa profilaggrin polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form monomeric filaggrin (37 kDa), which binds to and condenses the keratin cytoskeleton and thereby contributes to the cell compaction process that is required for squame biogenesis. Within the squames, filaggrin is citrullinated, which promotes its unfolding and further degradation into hygroscopic amino acids, which constitute one element of natural moisturising factor. Loss of profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis), which is also prone to water loss (xerosis). Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens. Filaggrin is therefore in the frontline of defence, and protects the body from the entry of foreign environmental substances that can otherwise trigger aberrant immune responses.

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“…(41)(42)(43)(44) Genetic associations of FLG mutations with AD were confirmed and further verified by many independent groups using numerous cohorts of different populations e.g. American, (45) Caucasian and Northern-American AD, (2) European and Asian ancestry, (43,(46)(47)(48)(49)(50)(51) Chinese, (52) German, (53) Irish, (43) and Japanese. (54) More than 40 FLG loss-of-function mutations have been described in Europeans and Asians.…”

Section: -Filaggrin Genementioning

confidence: 67%

Molecular Genetic of Atopic Dermatitis : An Update

Al‐Shobaili

Ahmed

Alnomair

et al. 2016

IJHS

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Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date.

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Filaggrin null mutations and childhood atopic eczema: A population-based case-control study

Abstract: FLG null mutations are significantly associated with mild-to-moderate atopic eczema in childhood, with a recessive pattern of inheritance.

Cited by 142 publications

References 38 publications

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk

Filaggrin in the frontline: role in skin barrier function and disease

Molecular Genetic of Atopic Dermatitis : An Update

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