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.

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A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.

Ethnic differences may affect the association of adiponectin (Ad) multimers with coronary artery disease (CAD). We analyzed the associations of total Ad, Ad multimers, and T45G polymorphism of ADIPOQ gene with pre‐existing CAD. We carried out a cross‐sectional study of 216 Afro‐Caribbean type 2 diabetic (T2D) subjects. Levels of total Ad, high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) isoforms were measured. Subjects were genotyped. Of the subjects studied, 57 had pre‐existing CAD, 77% of whom have had myocardial infarction. Subjects with CAD had lower Ad levels (total and multimers) and a higher frequency carried the minor allele 45G, GG/TG, (18% vs. 8%, P = 0.03) than subjects without CAD. In logistic regression analysis, the models used evaluate Ad in the context of adjustment for metabolic syndrome characteristics. The adjusted odds ratio (OR) of CAD was increased significantly (by factors of 1.05–3.27) for males, older subjects, low high‐density lipoprotein cholesterol (HDL‐C), high triglycerides (TGs), and carriers of the 45 G allele. For Ad, in model 1 (including only total Ad) the adjusted OR was 2.30; P = 0.03 and, in model 2 (including the three multimers, but not total Ad), the adjusted ORs were 0.73; P = 0.52 (HMW), 2.90; P = 0.01 (MMW), and 2.08; P = 0.09 (LMW). The T45G polymorphism in the ADIPOQ gene and hypoadiponectinemia were associated with CAD in our T2D subjects of predominantly African background. This effect of Ad level was mainly related to the MMW Ad form.

This was consistent with a lack of effect on clinical renal outcomes found in previous studies and showed that even replicated and biologically plausible genetic association studies based on surrogate markers do not easily translate into clinically meaningful prognosis.

Aims/Introduction: The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (-11391G>A) and rs182052 (-10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry. Materials and Methods: A cross-sectional study of 200 patients was carried out. Concentrations of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms were measured. The four polymorphisms were genotyped. Results: Decreased values were noted for total Ad in overweight, dyslipidemia and coronary artery disease (CAD), for HMW in overweight and dyslipidemia, for MMW in CAD, for LMW in dyslipidemia and CAD, for the percentage HMW/total in overweight, and for MMW:HMW ratio in patients without hypertriglyceridemic waist (HTGW). Significant associations were noted between total Ad, HMW, and HMW/total Ad and rs182052 under a dominant model (P = 0.04, P = 0.03 and P = 0.04, respectively), and between MMW and rs17300539 (P = 0.006). No significant difference in adiponectin concentrations was noted according to rs2241766 and rs1501299 genotypes. Patients carrying the rs2241766 G allele (TG+GG) had an increased risk of HTGW (odds ratio [OR] 3.1; P = 0.04) and of CAD (OR 3.3; P = 0.01). The odds of having low total adiponectin concentrations (<25th percentile: 3.49 ng/mL) for carrying the rs182052A allele (AA+GA) was: OR 0.40; P = 0.009. The single-nucleotide polymorphism associated with adiponectin levels was not concomitantly associated with cardiometabolic risk factors. Conclusions: Adiponectin concentrations and ADIPOQ variants are implicated in the pathophysiological process leading to cardiovascular diseases, but the genetic effects seem to be independent of adiponectin concentrations in our Afro-Caribbean diabetic patients.