Relationship between the FTO Genotype and Early Chronic Kidney Disease in Type 2 Diabetes: The Mediating Role of Central Obesity, Hypertension, and High Albuminuria

Abstract

<b><i>Introduction:</i></b> Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (<i>FTO</i>) 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 <i>FTO</i> gene and early chronic kidney disease (CKD) in individuals with T2D. <b><i>Methods:</i></b> 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 <i>FTO</i> gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. <b><i>Results:</i></b> Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (<i>C</i>) was higher among participants with CKD (21.8 vs. 10.8%; <i>p</i> = 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 <i>FTO</i> gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. <b><i>Conclusions:</i></b> These findings suggest that the <i>C</i> allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.