Genetic Variants Flanking the FGF21 Gene Were Associated with Renal Function in Chinese Patients with Type 2 Diabetes

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.

Fibroblast Growth Factor 21 Predicts Short-Term Prognosis in Patients With Acute Heart Failure: A Prospective Cohort Study

“…Previous studies had shown that FGF21 play an important role in renal function, patients with renal impairment tend to have higher levels of FGF21 than normal individuals, and the higher the concentration of FGF21 in patients, the poorer the renal function ( 34 – 36 ). A recent study showed that mutations in FGF21-adjacent genes are associated with eGFR in Chinese diabetic patients ( 37 ), indicating the importance of FGF21 in renal function in some disease states. What role and how FGF21 plays in the kidneys is still no clear, but large studies had confirmed the protective effect of FGF21 in the kidneys.…”

The Multiple Roles of Fibroblast Growth Factor in Diabetic Nephropathy

“…However, with the development of DN, renal function is decreased, leading to the accumulation of FGF21 in the body. [85][86][87] Therefore, the circulating FGF21 levels are considered as a potential biomarker for predicting the development of DN. 86,[88][89][90] Administration of FGF21 can reduce nephritis, oxidative stress, fibrosis and lipid accumulation caused by diabetes, which reduce kidney cell apoptosis and protect the kidney.…”

“…[85][86][87] Therefore, the circulating FGF21 levels are considered as a potential biomarker for predicting the development of DN. 86,[88][89][90] Administration of FGF21 can reduce nephritis, oxidative stress, fibrosis and lipid accumulation caused by diabetes, which reduce kidney cell apoptosis and protect the kidney. [91][92][93][94] FGF21 ameliorates DN by improving insulin resistance.…”

Regulation and Potential Biological Role of Fibroblast Growth Factor 21 in Chronic Kidney Disease

“…Moreover, a metaanalysis found that FGF21 level in the plasma of type 2 diabetes patients significantly increased compared with the control group, which was affected by the variables of body mass index (BMI), total cholesterol and triglycerides (Wang et al, 2019). There is evidence existing to support that genetic variation in the FGF21 gene region is related to the renal function of type 2 diabetes patients and affects the eGFR of diabetic patients (Yu et al, 2019).…”