title: A polymorphism at the IL6ST (gp130) locus is associated with traits of the metabolic syndrome.
abstract: 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.
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gottardo
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Christine
authors.initials: C
authors.lastname: Powers
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.forename: Maria C
authors.initials: MC
authors.lastname: Marescotti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
mesh_terms: D000328:Adult; D050822:Cytokine Receptor gp130 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D050822:Cytokine Receptor gp130; D005947:Glucose