A polymorphism at the IL6ST (gp130) locus is associated with traits of the metabolic syndrome

The interleukin 6 signal transducer (IL6ST, also known as gp130) is a ubiquitously expressed intermediate of the interleukin-6 signaling pathway. We investigated whether genetic variability at the IL6ST locus is involved in the modulation of metabolic traits and the etiology of the metabolic syndrome (MS). Four haplotype-tagging single nucleotide polymorphisms were typed in two populations of non-diabetic subjects, one from Northern Italy (Padua (PD), n 630), the other from Southern Italy (San Giovanni Rotondo (SGR), n 553). In the PD population, a nominally significant association was observed between fasting glucose and rs715180 (P 0.02), rs3729960 (P 0.02), and rs10940495 (P 0.05), between homeostasis model assessment index (HOMA(IR)) and rs715180 (P 0.04), and between triglycerides and rs3729960 (P 0.03). In the SGR population, high-density lipoprotein (HDL) levels were associated with rs715180 (P 0.01), systolic blood pressure and waist circumference with rs3729960 (P 0.005 and 0.02, respectively). The frequency of rs715180 minor allele carriers progressively decreased from individuals with no MS components to those with three or more components (P for trend 0.006 in the two populations combined). Compared to major allele homozygotes, minor allele carriers had 40 lower odds of having at least one MS component (Odds ratio 0.6, 95 confidence interval 0.4-0.8, P 0.005). These findings point to IL6ST variants as possible determinants of impaired glucose metabolism and other abnormalities of MS.