Abstract
Aims Fibroblast growth factor 21 (FGF21) is closely linked with metabolic disorders including diabetes. Evidences suggested that FGF21 may play a protective role against diabetic kidney disease (DKD). However, the relationship between genetic variants in the FGF21 gene region and DKD remains unknown. In our study, we aimed to investigate the association of genetic variations in this gene region with DKD and DKD-related clinical traits. Materials and Methods We recruited 1340 Han Chinese participants with type 2 diabetes, including 596 DKD patients and 744 patients who was diagnosed with diabetes for more than 5 years but did not progress to DKD. Three single-nucleotide polymorphisms were selected (rs2071699, rs838136, and rs499765) and genotyped. The association between these SNPs and DKD as well as DKD-related quantitative traits was analyzed. Results We did not find any significant association between these SNPs and susceptibility to DKD in the present study. However, a significant association with estimated glomerular filtration rate (eGFR) was detected: in the non-DKD group, rs838136 was significantly associated with eGFR under an additive model (β = 0.013 ± 0.006, P = 0.0295, β was calculated for log10eGFR) as well as a recessive model (P = 0.0385) and rs499765 was associated with eGFR under a dominant model (P = 0.0411) and in the DKD group, rs499765 showed a trend toward association with eGFR under an additive model (β = −0.022 ± 0.012, P = 0.0820, β was calculated for log10eGFR) and showed a significant association with eGFR under a dominant model (P = 0.0182). Conclusions Our findings indicated that genetic variations adjacent to FGF21 were associated with eGFR in Chinese diabetic patients.
Highlights
Diabetes has become one of the most common chronic diseases in the world, and the prevalence of the disease has experienced an exploding increase in recent years, especially in the Chinese population [1]
A recent study compared the therapeutic effect of rhFGF21 and PEG-rhFGF21 on diabetic nephropathy in diet-induced obesity (DIO) mice, and the results showed that PEG-rhFGF21 was more efficacious in ameliorating functional and morphological abnormalities induced by diabetic nephropathy in db/db and DIO mice [11]
The albuminuria level was measured using the samples from 24-hour urine collection, which was repeated in three consecutive days, and the mean values were used for further analysis. estimated glomerular filtration rate (eGFR) was calculated by using a Chinese population-specific formula derived from the Modification of Diet in Renal Disease (MDRD) equation [12]
Summary
Diabetes has become one of the most common chronic diseases in the world, and the prevalence of the disease has experienced an exploding increase in recent years, especially in the Chinese population [1]. FGF21 is an endocrine member of the fibroblast growth factor (FGF) gene family, predominantly expressed in the liver It exerts beneficial metabolic effects in animal models, such as reducing blood glucose and triglyceride levels, increasing insulin sensitivity, suppressing hepatic glucose production, increasing expenditure, and losing weight [5,6,7,8]. It is recognized as a novel metabolic regulator, and its therapeutic potential has been suggested for the treatment of metabolic disorders including diabetes and obesity
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