DUSP1 gene polymorphisms are associated with obesityrelated metabolic complications and gene methylation levels in severely obese patients

Abstract

DUSP1 is a member of the dual‐specificity phosphatase family involved in the regulation of innate immune function and inflammation. In a previous study, DUSP1 gene was found to be underexpressed in visceral adipose tissue from severely obese men with the metabolic syndrome.ObjectiveTo verify the association between DUSP1 polymorphisms, gene expression and methylation levels and obesity‐related metabolic complications.MethodsAssociation of tagging SNPs (tSNPs) with obesity‐related complications was tested in a cohort of 1900 severely obese individuals. Impact of tSNPs on CpG site methylation and correlations between DNA methylation and gene expression were computed in a subset of 14 samples.ResultsFollowing adjustment for the effects of age, sex and BMI, heterozygotes for rs881150 had lower HDL‐cholesterol levels and homozygotes for rs13184134 and rs7702178 had increased fasting glucose levels. rs13184134 was associated with methylation levels of CpG sites located ~1800 bp upstream the transcription start site. Methylation levels for 3 CpG sites located in this region were inversely correlated with DUSP1 gene expression.ConclusionThese results suggest that polymorphisms in DUSP1 modulate plasma glucose and HDL‐cholesterol levels in obese patients potentially through alterations of gene methylation and expression. Funding: CIHR