Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Diabetologia. 2010 Feb;53(2):234-46. doi: 10.1007/s00125-009-1517-2. Epub 2009 Sep 1.
AIMS/HYPOTHESIS: Resistin is a cytokine derived from adipose tissue and is implicated in obesity-related insulin resistance and type 2 diabetes mellitus. Polymorphisms of the resistin gene (RETN) have been shown to affect the plasma resistin concentration. The aims of this study were to identify polymorphisms of RETN that influence plasma resistin concentration and to clarify the relation between plasma resistin level and metabolic disorders in an aged Japanese cohort.
The study participants comprised 3133 individuals recruited to a population-based prospective cohort study (KING study). Plasma resistin concentration, BMI, abdominal circumference, blood pressure, fasting plasma glucose and serum insulin concentrations, HbA(1c) content and serum lipid profile were measured in all participants. The HOMA index of insulin resistance (HOMA-IR) was also calculated. Eleven polymorphisms of RETN were genotyped.
A combination of ANOVA and multiple linear regression analysis in screening and large-scale subsets of the study population revealed that plasma resistin concentration was significantly associated with rs34861192 and rs3745368 polymorphisms of RETN. Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI.
CONCLUSIONS/INTERPRETATION: Our results implicate the rs34861192 and rs3745368 polymorphisms of RETN as robust and independent determinants of plasma resistin concentration in the study population. In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity.
ClinicalTrials.gov NCT00262691.
目的/假设：抵抗素是一种来源于脂肪组织的细胞因子，与肥胖相关的胰岛素抵抗和 2 型糖尿病有关。抵抗素基因（RETN）的多态性已被证明会影响血浆抵抗素浓度。本研究的目的是确定影响血浆抵抗素浓度的 RETN 多态性，并阐明在一个日本老年队列中，血浆抵抗素水平与代谢紊乱之间的关系。
本研究的参与者包括 3133 名参加基于人群的前瞻性队列研究（KING 研究）的个体。所有参与者均测量了血浆抵抗素浓度、BMI、腰围、血压、空腹血糖和血清胰岛素浓度、HbA(1c)含量和血清脂质谱。还计算了胰岛素抵抗的 HOMA 指数（HOMA-IR）。对 RETN 的 11 个多态性进行了基因分型。
在筛选和研究人群的大样本子集的 ANOVA 和多元线性回归分析中，发现血浆抵抗素浓度与 RETN 的 rs34861192 和 rs3745368 多态性显著相关。对年龄和性别进行调整的多元线性回归分析也表明，血浆抵抗素水平与血清高密度脂蛋白胆固醇、三酰甘油和胰岛素浓度以及 BMI 显著相关。
结论/解释：我们的研究结果表明，RETN 的 rs34861192 和 rs3745368 多态性是研究人群中血浆抵抗素浓度的稳健且独立的决定因素。此外，血浆抵抗素水平与血脂异常、血清胰岛素浓度和肥胖有关。
ClinicalTrials.gov NCT00262691。
