Introduction: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D. Methods: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. Results: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. Conclusions: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.
Lifestyle Genomics

中文翻译：

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FTO 基因型与 2 型糖尿病早期慢性肾脏病的关系：中枢性肥胖、高血压和高蛋白尿的中介作用

简介：脂肪量和肥胖相关 ( FTO ) 基因中的单核苷酸多态性 (SNP) 与 2 型糖尿病 (T2D) 及其并发症有关。本研究的目的是调查哪些以及如何（直接或间接）临床和代谢变量介导 T2D 患者脂肪量与FTO基因与早期慢性肾病 (CKD) 之间的关联。方法：这项横断面研究在 236 名 T2D 参与者的样本中进行（53.4% 的女性，平均年龄 60 ± 10 岁）。在FTO中对 DNA 样本进行 rs7204609 多态性 (C/T) 基因分型基因。收集临床、人体测量学和代谢数据。路径分析用于评估关联。结果：在样本中，78 名 T2D 患者患有 CKD（33%）。CKD 参与者中风险等位基因 ( C ) 的存在较高（21.8% 对 10.8%；p = 0.023）。这种多态性与较高的腰围呈正相关，而腰围又与较高的糖化血红蛋白和较高的血压相关。较高的血压水平与较高的尿白蛋白排泄（UAE）相关，正如预期的那样，较高的UAE与CKD相关。路径分析显示FTO基因与早期 CKD之间存在间接关系，由腰围、血压水平和阿联酋介导。结论：这些发现表明， C等位基因可能通过存在向心性肥胖、高血压和高蛋白尿导致 T2D 个体对 CKD 的遗传易感性。
生活方式基因组学