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

A 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.rs7849191 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.It 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.The metabolic syndrome (MS) is a constellation of cardiometabolic risk factors including central obesity, insulin resistance (IR), hypertension, hyperglycemia, and dislipidemia [1,2]. Insulin resistance (IR) is probably the principal cause of the MS [3,4]. Over the past decades, a sustained worldwide increase in the incidence of MS has taken place, associated with the global epidemic of obesity and type 2 Diabetes Mellitus (DM2) [5].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]. Suppressor of cytokine signaling (SOCS) proteins are known to act as negative regulators of cytokine action via inh