Polymorphisms in the interleukin‐6 receptor gene are associated with body mass index and with characteristics of the metabolic syndrome

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Abstract
Summary: Objective  Low‐grade inflammation has been related to obesity, insulin resistance and the metabolic syndrome. The Asp358Ala variant and the CA‐repeat polymorphism in the interleukin‐6 receptor (IL‐6R) gene have been reported to be associated with obesity in Pima Indians and Spanish women, respectively. The aim of this study was to investigate the association between these polymorphisms and obesity in a Mediterranean‐Caucasian population, and to determine whether this polymorphism was related to the metabolic syndrome as defined by the National Cholesterol Education Program – Adult Treatment Panel III (NCEP/ATP‐III) criteria.Design  Cross‐sectional.Patients  Three hundred and ninety subjects from the general population.Methods  The Asp358Ala and CA‐repeat polymorphisms were analysed by polymerase chain reaction (PCR) amplification, followed by restriction fragment length polymorphism or capillary electrophoresis, respectively.Results  Both polymorphisms were in strong linkage disequilibrium, Asp358 alleles being associated with 149 CA‐repeat alleles (χ2 = 76·275, P < 0·0001). Therefore, only the association of the Asp358Ala variant with obesity and the metabolic syndrome was assessed in the whole series of subjects. Subjects homozygous for Asp358 alleles had statistically higher body mass index (BMI) compared with Ala358 carriers (27·7 ± 5·41 vs. 26·6 ± 4·96 kg/m2; P < 0·05). Moreover, the prevalence of the metabolic syndrome was significantly higher in carriers of the Asp358 allele compared with Ala358 homozygotes (12·7%vs. 0·0%; P = 0·01). This relationship remained significant after adjusting for age, insulin resistance, sex and BMI.Conclusions  The Asp358Ala and CA‐repeat polymorphisms in the IL‐6R gene are associated with obesity and characteristics of the metabolic syndrome in our population of Mediterranean subjects.
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