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Variants of the Interleukin-10 Promoter Gene Are Associated With Obesity and Insulin Resistance but Not Type 2 Diabetes in Caucasian Italian Subjects

¹ Department of Experimental and Clinical Medicine, University Magna Grjcia of Catanzaro, Catanzaro, Italy
² Department of Internal Medicine, University of Rome-Tor Vergata, Rome, Italy
³ Unità di Diabetologia ed Endocrinologia, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

Address correspondence and reprint requests to Giorgio Sesti, MD, Dipartimento di Medicina Sperimentale e Clinica, Policlinico Mater Domini, Via Tommaso Campanella 88100, Catanzaro, Italy. E-mail: sesti{at}unicz.it

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance; IL, interleukin

Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been associated with obesity and type 2 diabetes. The three polymorphisms –1082G/A, –819C/T, and –592C/A in the IL10 promoter were reported to influence IL10 transcription. We investigated whether these polymorphisms were associated with type 2 diabetes and related traits in a cohort of Italian Caucasians comprising 551 type 2 diabetic and 1,131 control subjects. The –819C/T and –592C/A polymorphisms were in perfect linkage disequilibrium (r² = 1.0). The –1082G/A polymorphism was not associated with type 2 diabetes or related traits. Although the –592C/A polymorphism was not associated with type 2 diabetes, nondiabetic homozygous carriers of the A allele showed increased BMI and insulin resistance and lower plasma IL-10 levels compared with the other genotypes. In the nondiabetic group, the ATA haplotype was associated with an increased risk for obesity (odds ratio 1.28 [95% CI 1.02–1.60]; P = 0.02). The ATA/ATA composite genotype was associated with an increased risk for obesity (1.96 [1.16–3.31]; P = 0.01) and insulin resistance (1.99 [1.12–3.53]; P = 0.01). This study suggests that polymorphisms and haplotypes of the IL10 promoter may be associated with obesity and insulin resistance in a large sample of Italian Caucasians.

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