The effect of diabetes and the diabetogenic TBC1D4 p.Arg684ter variant on kidney function in Inuit in Greenland

Int J Circumpolar Health. 2023 Dec;82(1):2191406. doi: 10.1080/22423982.2023.2191406.

Abstract

The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting. Health survey data and TBC1D4 genotypes from 5,336 Greenlanders were used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR <60 ml/min/1.73m2), comparing individuals with and without diabetes, including the effect of TBC1D4 variant. Of the 3,909 participants with complete data, 9.3% had diabetes. Albuminuria was found in 27.6% and 9.5% and CKD was found in 10.8% and 6.3% among those with and without diabetes, respectively. Diabetes was cross-sectionally associated with an increased risk of albuminuria (OR (95% CI) = 2.37 (1.69,3.33); p < 0.001) and the TBC1D4 variant protected against albuminuria (OR (95% CI) = 0.44 (0.22,0.90); p = 0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. Diabetes conferred an increased risk of albuminuria, and the TBC1D4 variant was associated with a decreased risk of albuminuria, but neither was associated with CKD. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.

Keywords: CKD; Greenland; complications; diabetes; genetics.

MeSH terms

  • Albuminuria / complications
  • Diabetes Mellitus* / genetics
  • GTPase-Activating Proteins* / genetics
  • Greenland / epidemiology
  • Humans
  • Inuit / genetics
  • Kidney
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / genetics

Substances

  • GTPase-Activating Proteins
  • TBC1D4 protein, human