Journal Article

Association of <i>ADIPOQ</i> genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes

Riphed Jaziri, Roberte Aubert, Ronan Roussel, Nathalie Emery, Suliya Maimaitiming, Naïma Bellili, Aurélie Miot, Pierre-Jean Saulnier, Florence Travert, Samy Hadjadj, Michel Marre and Frédéric Fumeron

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 7, pages 2231-2237
Published in print July 2010 | ISSN: 0931-0509
Published online January 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfp771
Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes

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Background. Adiponectin levels are high in cases of diabetic nephropathy, but it remains unclear whether these high levels are a cause or a consequence of the disease. We investigated the possible association of polymorphisms in the adiponectin gene and baseline adiponectin levels with the incidence of renal events in subjects with type 2 diabetes.

Methods. We studied three adiponectin polymorphisms (−11391G > A, +45T > G and +276G > T) in 3086 subjects with type 2 diabetes and high levels of albumin excretion from the diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events and ramipril (DIABHYCAR) trial. Baseline concentrations of total adiponectin and of adiponectin isoforms were determined in cases with incident renal events and in controls matched for sex, age, body mass index (BMI) and adiponectin genotype. We used another cohort of type 2 diabetes patients—the survie, diabète de type 2 et génétique(SURDIAGENE) study (n = 1004)—for the replication of genetic data.

Results. In DIABHYCAR, the −11391A and +45G alleles were associated with a higher incidence of renal events [hazard ratio (HR) = 1.73; 95% confidence interval (CI), 1.10–2.71; and HR = 1.68; 95% CI, 1.14–2.47, respectively]. The haplotype containing susceptibility alleles, −11391A/+45G/+276G, was more frequent in cases with renal events (5.1% vs. 1.9% in those without, P = 0.005). In SURDIAGENE, the −11391A/+45G/+276G haplotype was also associated with renal events (5.6% vs. 1.9% in those without, P = 0.03). In DIABHYCAR, all isoforms were more abundant in subjects carrying the −11391A or +45G alleles. Medium- (MMW) and low-molecular weight (LMW) isoforms were more abundant in cases with renal events.

Conclusions. In subjects with type 2 diabetes and early renal dysfunction, adiponectin gene variants are determinants of the renal risk. The −11391A and +45G alleles may affect renal risk by leading to high circulating adiponectin concentrations, at least those of MMW and LMW isoforms.

Keywords: adiponectin; genetic polymorphisms; nephropathy; prospective study; type 2 diabetes

Journal Article.  4641 words. 

Subjects: Nephrology

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