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

Maria Overvad*, Lars Jorge Díaz, Peter Bjerregaard, Michael Lynge Pedersen, Christina Viskum Lytken Larsen, Niels Grarup, Torben Hansen, Peter Rossing, Marit Eika Jørgensen

*Corresponding author for this work

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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.

Original languageEnglish
Article number2191406
JournalInternational Journal of Circumpolar Health
Volume82
Issue number1
Number of pages8
ISSN1239-9736
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
MEJ has received research grants from Sanofi Aventis, Boehringer Ingelheim (jeg har kun opgivet de sidste 36 mnd). MEJ holds shares in Novo Nordisk AS.

Keywords

  • CKD
  • complications
  • diabetes
  • genetics
  • Greenland

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