Association of common variants in JAK2 gene with reduced risk of metabolic syndrome and related disorders.

Alberto Penas-Steinhardt,Fernando Brites,Gustavo D Frechtel,Leonardo Gomez-Rosso,Mariana L Tellechea,Edgardo Poskus

doi:10.1186/1471-2350-12-166

Abstract

BackgroundDisturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects.MethodsA total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis.Resultsrs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis.ConclusionsIt was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling.

Highlights

Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease
We examined the association between two single nucleotide polymorphisms (SNPs) of Janus kinase 2 (JAK2) and MS, phenotypes and quantitative traits related to MS in a sample of 724 unrelated men
We observed association of rs3780378 with both TG values under 150 mg/dl and HW; and we demonstrated differences in TG, TG/HDL-C and lipid accumulation product (LAP) between genotypes at levels that take into account multiple testing

Summary

Introduction

Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. The metabolic syndrome (MS) is a constellation of cardiometabolic risk factors including central obesity, insulin resistance (IR), hypertension, hyperglycemia, and dislipidemia [1,2]. Janus kinase 2 (JAK2) is a nonreceptor tyrosine kinase recruited by receptors that lack intrinsic kinase activity [6]. The JAK/STAT (signal transducer and activator of transcription) pathway transmits a wide range of cytoplasmic signals from cytokines, growth factors and hormones that bind to specific cell surface receptors [7]. There is a growing body of evidence that supports a role for specific SOCS members in the development of IR [8]

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