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The genetic side of diabetic kidney disease: a review

  • Nephrology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Diabetic kidney disease (DKD) is one of the most common complications of diabetes, with approximately 30–40% of patients with type 1 diabetes mellitus and 20% of patients with type 2 diabetes mellitus eventually developing DKD. If DKD is not controlled in the early clinical stage and proteinuria develops, the disease will progress to end-stage renal disease. The pathogenesis of DKD remains largely unknown and is multifactorial, likely due to interactions between genetic and environmental factors. Familial clustering also supports a critical role of hereditary factors in DKD. The development of gene detection technology has promoted the exploration of DKD susceptibility genes in different cohorts of patients with diabetes. Identifying susceptibility genes can provide insights into the pathogenesis of DKD, as well as a basis for its clinical diagnosis and therapy.

Results

Numerous candidate gene loci have been found to be associated with DKD, many of which play critical regulatory roles in the pathogenesis of this disease, including genes involved in glycol-metabolism, lipid metabolism, the renin–angiotensin–aldosterone system, inflammation and oxidative stress. In this review, we summarize the functions of several susceptibility genes involved in the development of DKD.

Conclusion

Based on our findings, we recommend that studying susceptibility gene polymorphisms can lead to a better understanding of the pathogenesis of DKD and could help prevent this disease or improve its outcomes.

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Abbreviations

DKD:

Diabetic kidney disease

T2DM:

Type 2 diabetes mellitus

ESRD:

End-stage renal disease

ACE:

Angiotensin (Ang)-converting enzyme

ALR2:

Aldose reductase 2

APOC1:

Apolipoprotein C1

APOE:

Apolipoprotein E

EPO:

Erythropoietin

HSPG2:

Heparan sulfate proteoglycan 2

FRMD3:

FERM domain-containing protein 3

CARS:

Chimeric antigen receptors

UNC13B:

Unc-13 homolog B

CPVL:

Cystic periventricular leukomalacia

NOS3:

Nitric oxide synthase3

VEGF:

Vascular endothelial growth factor

GREM1:

Gremlin 1

ELMO1:

Engulfment and cell motility 1

CCR5:

Chemokine receptor 5

CNDP1:

Carnosine dipeptidase 1

CCL2:

Chemokine ligand 2

IL1:

Interleukin-1

MMP9:

Matrix metallopeptidase 9

ADIPOQ:

Adiponectin

AGT:

Angiotensinogen

AGTR1:

Angiotensinogen receptor 1

GKRP:

Glucokinase regulatory protein

eGFR:

Estimated glomerular filtration rate

SLC12A3:

Solute carrier family 12 member 3

ACACB:

Acetyl-CoA carboxylase beta

ACC2:

Acetyl-CoA carboxylase 2

VNTR:

Variable number of tandem repeats

MTHFR:

Methylenetetrahydrofolate reductase

PPARγ:

Peroxisome proliferator-activated receptor-γ

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Acknowledgements

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Funding

This work was supported by the Jiangsu Research Hospital Association for Precision Medication (No. JY202011), Hospital Pharmaceutical Research Project of Jiangsu Pharmaceutical Association and Tianqing (No. Q2019096) and Wuxi Science and Technology Development Medical and Health Guidance Project (No. CSZ0N1809). The authors declare that they have no financial relationship with the organization that sponsored the research, and the funding body was not involved in study design, data collection, analysis and writing of the study.

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Authors and Affiliations

  1. Department of Pharmacy, Affiliated Hospital of Jiangnan University, Jiangsu Province, Wuxi, China

    Jinfang Song

  2. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China

    Jinfang Song & Xiaoxing Yin

  3. Wuxi School of Medicine, Jiangnan University, Wuxi, China

    Jiang Ni

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  1. Jinfang Song
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J-FS: wrote the manuscript. JN and X-XY: revised the manuscript. All the authors reviewed, considered and approved the manuscript. All the authors contributed substantially to the work presented in this paper, read and approved the final manuscript.

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Song, J., Ni, J. & Yin, X. The genetic side of diabetic kidney disease: a review. Int Urol Nephrol 55, 335–343 (2023). https://doi.org/10.1007/s11255-022-03319-w

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