INSERM, UMR-S 1138, Centre de Recherches des Cordeliers, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, Paris, France.
Nephrol Dial Transplant. 2017 Dec 1;32(12):1987-1993. doi: 10.1093/ndt/gfx071.
High plasma adiponectin levels are associated with diabetic nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be associated with adiponectin levels. We investigated associations between allelic variations of CDH13 and DN in subjects with type 1 diabetes.
Two CDH13 polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up), 'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and 'Génétique de la Néphropathie Diabétique' (GENEDIAB) (n = 456, 9-year follow-up for n = 283) cohorts. Adiponectin levels were measured in plasma samples from GENESIS and GENEDIAB cohorts.
Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor allele of rs3865188 was associated with lower adiponectin levels (P = 0.006). rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P = 0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with baseline prevalence of established/advanced DN. These polymorphisms were also associated with the risk of ESRD (0.006 < P < 0.03). The association between rs11646213 (but not rs3865188) and renal function remained significant after adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR) 1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P = 0.04) were associated with risk of renal events (defined as progression to more severe DN stages).
Plasma adiponectin levels are associated with the prevalence of DN and the incidence of ESRD in patients with type 1 diabetes. CDH13 polymorphisms are also associated with the prevalence and incidence of DN, and with the incidence of ESRD in these patients. The association between CDH13 and DN may be due to pleiotropic effects, both dependent and independent of plasma adiponectin levels.
高血浆脂联素水平与糖尿病肾病（DN）有关。T-钙粘蛋白基因（CDH13）的变异与脂联素水平有关。我们研究了 CDH13 等位基因变异与 1 型糖尿病患者中 DN 的相关性。
在来自“生存遗传肾病”（SURGENE）（n=340，10 年随访）、“法国-比利时基因”（GENESIS）（n=501，462 名患者的 5 年随访）和“糖尿病肾病遗传”（GENEDIAB）（n=456，283 名患者的 9 年随访）队列的 1297 名 1 型糖尿病患者中分析了两个 CDH13 多态性。在 GENESIS 和 GENEDIAB 队列的血浆样本中测量了脂联素水平。
GENEDIAB 和 GENESIS 研究的合并分析表明，纳入时已确诊/晚期 DN 的患者（P<0.0001）和随访时发生终末期肾病（ESRD）的患者（P<0.0001）的基线血浆脂联素水平较高。rs3865188 的次要等位基因与较低的脂联素水平相关（P=0.006）。rs11646213 [比值比（OR）1.47；95%置信区间（CI）1.18-1.85；P=0.0009]和 rs3865188（OR 0.71；95%CI 0.57-0.90；P=0.004）与基线已确诊/晚期 DN 的患病率相关。这些多态性也与 ESRD 风险相关（0.006<P<0.03）。rs11646213（但不是 rs3865188）与肾功能的相关性在调整血浆脂联素后仍然显著。在 SURGENE 中，rs11646213 [风险比（HR）1.69；95%CI 1.01-2.71；P=0.04]和 rs3865188（HR 0.74；95%CI 0.55-0.99；P=0.04）与肾脏事件的风险（定义为进展为更严重的 DN 阶段）相关。
血浆脂联素水平与 1 型糖尿病患者中 DN 的患病率和 ESRD 的发生率相关。CDH13 多态性也与 DN 的患病率和发生率以及这些患者中 ESRD 的发生率相关。CDH13 与 DN 之间的相关性可能是由于多效性，依赖于和独立于血浆脂联素水平。
