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Title

Association of Polymorphisms in the Interleukin 6 Receptor Complex with Obesity and Hyperandrogenism

AuthorsEscobar-Morreale, Héctor F.; Calvo, Rosa M. CSIC; Villuendas, Gemma; Sancho, José; San Millán, José L.
KeywordsIL6R
Gp130
Insulin resistance
Polycystic ovary syndrome
Metabolic syndrome
Issue DateAug-2003
PublisherNorth American Association for the Study of Obesity
CitationObesity Research 11(8): 987-996 (2003)
AbstractObjective: Interleukin-6 (IL-6), is an inflammatory cytokine that may influence the pathogenesis of obesity and hyperandrogenism. IL-6 exerts its actions through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130). Genetic variability at these loci might contribute to explain the development of obesity and hyperandrogenism. Research Methods and Procedures: We have evaluated the possible association of several polymorphisms in the IL6R-alpha and gp130 genes with obesity and/or hyperandrogenism in a case-control study involving 143 hyperandrogenic patients and 45 healthy women from Spain. Results: A microsatellite CA-repeat polymorphism in the IL6R-alpha locus was associated with obesity. The frequency of the common 149-bp allele was markedly increased in obese women compared with controls when considering patients and controls as a whole (0.41 vs. 0.29, chi2 = 17.085, p < 0.050). On the other hand, the uncommon Arg148 allele of the Gly148Arg polymorphism in the gp130 gene was more frequent in controls compared with hyperandrogenic patients (0.17 vs. 0.08, chi2 = 5.605, p = 0.026). Controls carrying Arg148 alleles had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations, a lower response of androstenedione to 1–24 adrenocorticotropin, and an almost significant decrease in free testosterone levels, suggesting that Arg148 alleles in the gp130 gene have a protective effect against androgen excess and adrenal hyperactivity. Discussion: Polymorphisms in the gp130 and IL6R-alpha loci influence hyperandrogenism and obesity, respectively. Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders.
Description10 pages, 5 tables.
Publisher version (URL)http://dx.doi.org/10.1038/oby.2003.136
URIhttp://hdl.handle.net/10261/24584
DOI10.1038/oby.2003.136
ISSN1071-7323
Appears in Collections:(IIBM) Artículos

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