Studio di associazione tra varianti genetiche comuni nel loci dell' Interleukin-6 signal trasducer (IL6ST) e del recettore della leptina (LEPR) e alcuni marcatori di insulino resistenza e di infiammazione
2008
The term metabolic syndrome refers to the variable clustering of abdominal obesity, impaired glucose tolerance, dyslipidemia, and high blood pressure. Together, these metabolic abnormalities are associated with a greatly increased risk of type 2 diabetes mellitus and cardiovascular disease. Growing evidence suggests that a state of chronic low-grade inflammation may contribute to such clustering of metabolic abnormalities and to their association with diabetes and increased atherosclerosis. While the molecular mechanisms underlying the link between inflammation and metabolic syndrome are not known, many studies point to proinflammatory cytokines released by the adipose tissue as possible mediators. The aim of our study was to examine whether genetic variability at the genetic loci of some of these molecules and their receptors can modulate metabolic and inflammatory traits in non diabetics subjects. Here we show the results regarding the interleukin 6 signal transducer (IL6ST, also known as gp130) and leptin receptor (LEPR) genes, two receptors sharing partial sequencing homology and similar structure. We first established the LD structure at the IL6ST and LEPR loci to select htSNPs comprehensively capturing genetic variability at these loci then we evaluate whether genetic variants at IL6ST and LEPR loci can modulate metabolic and inflammatory traits in two healthy population, one from Padova (PD, n=630) the other from San Giovanni Rotondo (SGR, n=553).
The IL6ST study points to some genetic variants as possible determinants of impaired glucose metabolism and other abnormalities of the metabolic syndrome, while the LEPR study, by finding that variability in the gene is a significant predictor of CRP and fibrinogen levels, lends further support to the hypothesis that leptin has a physiological influence on inflammatory and prothrombotic traits.
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