Nicolas A, Aubert R, Bellili-Muñoz N, Balkau B, Bonnet F, Tichet J, Velho G, Marre M, Roussel R, Fumeron F
Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France; Sorbonne Universités, UPMC Université Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 15, rue de l'École de Médecine, 75006 Paris, France.
Diabetes Metab. 2017 Feb;43(1):33-39. doi: 10.1016/j.diabet.2016.05.005. Epub 2016 Jun 8.
Adiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.
Two polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout.
In a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04-1.18; P=0.001) and 0.92 (95% CI: 0.87-0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R.
Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA, FLI and adiponectin levels persisted after adjusting for BMI.
CDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.
脂联素是一种由脂肪细胞分泌的与胰岛素敏感性相关的蛋白质。T-钙黏蛋白是高分子量和中分子量脂联素的受体。在全基因组关联研究（GWAS）中，T-钙黏蛋白基因（CDH13）多态性与循环脂联素水平相关。本研究在白种人群中调查了CDH13基因变异与2型糖尿病（T2D）及其相关参数之间的关联。
在两个法国队列中对CDH13的两个多态性位点（rs11646213和rs3865188）进行基因分型，一个是来自D.E.S.I.R.研究的普通人群（n = 5212），另一个是DIABHYCAR研究中的T2D患者（n = 3123）。在D.E.S.I.R.研究中，对基线血糖正常但3年后血糖升高的参与者（n = 230）以及整个过程中血糖一直正常的对照组（n = 226）测量基线脂联素水平。
在横断面分析中，患有和未患有T2D的人群中CDH13基因型分布不同，rs11646213和rs3865188的T2D比值比（OR）分别为1.11（95%可信区间：1.04 - 1.18；P = 0.001）和0.92（95%可信区间：0.87 - 0.98；P = 0.01）。与T2D较高OR相关的rs11646213变异，在D.E.S.I.R.研究参与者中还与较高的体重指数（BMI）（P = 0.03）和糖化血红蛋白（HbA）（P = 0.006）以及较低的血浆脂联素水平（P = 0.03）相关。相反，与T2D较低OR相关的rs3865188变异，还与较低的BMI（P = 0.03）、HbA（P = 0.02）和脂肪肝指数（FLI；P≤0.01）以及较高的血浆脂联素水平（P = 0.002）相关。在调整BMI后，与HbA、FLI和脂联素水平的关联仍然存在。
在这项法国人群研究中，CDH13多态性与T2D的患病率相关。这种关联可能通过对BMI和/或血浆脂联素的影响介导。
