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PLoS One. 2013 Dec 18;8(12):e84293. doi: 10.1371/journal.pone.0084293. eCollection 2013.

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

Author information

  • 1Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
  • 2Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark ; Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
  • 3National Allergy Research Centre, Department of Dermato Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
  • 4Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Hellerup, Denmark.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
24367652
[PubMed - indexed for MEDLINE]
PMCID:
PMC3867483
Free PMC Article
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