INSERM, U695, Genetic Determinants for Type 2 Diabetes and Its Vascular Complications, Paris, France.
Nephrol Dial Transplant. 2010 Jul;25(7):2231-7. doi: 10.1093/ndt/gfp771. Epub 2010 Jan 18.
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.
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.
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.
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.
在糖尿病肾病患者中，脂联素水平较高，但尚不清楚这些高水平是疾病的原因还是结果。我们研究了 2 型糖尿病患者中脂联素基因多态性和基线脂联素水平与肾脏事件发生的可能相关性。
我们研究了来自糖尿病、高血压、微量白蛋白尿或蛋白尿、心血管事件和雷米普利（DIABHYCAR）试验的 3086 例高白蛋白尿排泄量的 2 型糖尿病患者中的三种脂联素多态性（-11391G > A、+45T > G 和 +276G > T）。在发生肾脏事件的病例和性别、年龄、体重指数（BMI）和脂联素基因型匹配的对照组中，测定了总脂联素和脂联素同工型的基线浓度。我们使用另一个 2 型糖尿病患者队列——survie、diabète de type 2 et génétique（SURDIAGENE）研究（n = 1004）来复制遗传数据。
在 DIABHYCAR 中，-11391A 和 +45G 等位基因与肾脏事件的发生率较高相关[风险比（HR）= 1.73；95%置信区间（CI），1.10-2.71；和 HR = 1.68；95%CI，1.14-2.47]。含有易感性等位基因-11391A/+45G/+276G 的单倍型在发生肾脏事件的病例中更为常见（5.1%与无肾脏事件的病例中 1.9%相比，P = 0.005）。在 SURDIAGENE 中，-11391A/+45G/+276G 单倍型也与肾脏事件相关（5.6%与无肾脏事件的病例中 1.9%相比，P = 0.03）。在 DIABHYCAR 中，携带-11391A 或 +45G 等位基因的受试者所有同工型的含量均较高。中（MMW）和低分子量（LMW）同工型在发生肾脏事件的病例中更为丰富。
在 2 型糖尿病和早期肾功能障碍患者中，脂联素基因变异是肾脏风险的决定因素。-11391A 和 +45G 等位基因可能通过导致循环脂联素浓度升高，至少是 MMW 和 LMW 同工型的浓度升高，从而影响肾脏风险。
