No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.

<h4>Background</h4>Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized t...

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Autores principales:	Lise Lotte N Husemoen, Tea Skaaby, Torben Jørgensen, Jacob P Thyssen, Michael Meldgaard, Pal B Szecsi, Steen Stender, Jeanne Duus Johansen, Allan Linneberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29c7f2d290364ef7940f2bd50528f75a
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spelling	oai:doaj.org-article:29c7f2d290364ef7940f2bd50528f75a2021-11-18T08:41:14ZNo association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.1932-620310.1371/journal.pone.0084293https://doaj.org/article/29c7f2d290364ef7940f2bd50528f75a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24367652/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD), and all-cause mortality in the general population.<h4>Methods</h4>The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses.<h4>Results</h4>In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR) (95% confidence intervals (CI)) = 0.95 (0.73, 1.23), stroke (HR (95% CI) = 1.27 (0.97, 1.65), ischemic heart disease (HR (95%CI) = 0.92 (0.71, 1.19), and all-cause mortality (HR (95%CI) = 1.02 (0.83, 1.25)). Similar results were obtained when including prevalent cases in logistic regression models.<h4>Conclusion</h4>Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations.Lise Lotte N HusemoenTea SkaabyTorben JørgensenJacob P ThyssenMichael MeldgaardPal B SzecsiSteen StenderJeanne Duus JohansenAllan LinnebergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84293 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lise Lotte N Husemoen Tea Skaaby Torben Jørgensen Jacob P Thyssen Michael Meldgaard Pal B Szecsi Steen Stender Jeanne Duus Johansen Allan Linneberg No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
description	<h4>Background</h4>Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD), and all-cause mortality in the general population.<h4>Methods</h4>The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses.<h4>Results</h4>In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR) (95% confidence intervals (CI)) = 0.95 (0.73, 1.23), stroke (HR (95% CI) = 1.27 (0.97, 1.65), ischemic heart disease (HR (95%CI) = 0.92 (0.71, 1.19), and all-cause mortality (HR (95%CI) = 1.02 (0.83, 1.25)). Similar results were obtained when including prevalent cases in logistic regression models.<h4>Conclusion</h4>Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations.
format	article
author	Lise Lotte N Husemoen Tea Skaaby Torben Jørgensen Jacob P Thyssen Michael Meldgaard Pal B Szecsi Steen Stender Jeanne Duus Johansen Allan Linneberg
author_facet	Lise Lotte N Husemoen Tea Skaaby Torben Jørgensen Jacob P Thyssen Michael Meldgaard Pal B Szecsi Steen Stender Jeanne Duus Johansen Allan Linneberg
author_sort	Lise Lotte N Husemoen
title	No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
title_short	No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
title_full	No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
title_fullStr	No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
title_full_unstemmed	No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
title_sort	no association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/29c7f2d290364ef7940f2bd50528f75a
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No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.

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