Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes.
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.
Jaziri
Riphed
R
INSERM, U695, Genetic Determinants for Type 2 Diabetes and Its Vascular Complications, Paris, France.
Aubert
Roberte
R
Roussel
Ronan
R
Emery
Nathalie
N
Maimaitiming
Suliya
S
Bellili
Naïma
N
Miot
Aurélie
A
Saulnier
Pierre-Jean
PJ
Travert
Florence
F
Hadjadj
Samy
S
Marre
Michel
M
Fumeron
Frédéric
F
D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005602:France; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D012307:Risk Factors
D052242:Adiponectin; D020033:Protein Isoforms