Association of polymorphisms in the interleukin 6 receptor complex with obesity and hyperandrogenism.
OBJECTIVE
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.


METHODS
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, chi(2) = 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, chi(2) = 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.


CONCLUSIONS
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.
Escobar-Morreale
Héctor F
HF
Department of Endocrinology and. Department of Molecular Genetics, Hospital Ramón y Cajal, Carretera de Colmenar km. 9,100, 28034 Madrid, Spain. hector.escobar@uam.es
Calvo
Rosa M
RM
Villuendas
Gemma
G
Sancho
José
J
San Millán
José L
JL
D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D050822:Cytokine Receptor gp130; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019947:Receptors, Interleukin-6 / Q000235:genetics*
D015703:Antigens, CD; D001786:Blood Glucose; D006728:Hormones; C494199:IL6ST protein, human; D007328:Insulin; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; C113250:interleukin-6 receptor alpha; D050822:Cytokine Receptor gp130; D004247:DNA