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

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/1.73m(2)), 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.

Automated summary

The aim of this study was to investigate the impact of diabetes and the diabetogenic TBC1D4 variant on kidney function in a population-based setting in Greenland. Data from a health survey and TBC1D4 genotypes of 5,336 Greenlanders were analyzed to assess the odds ratios (ORs) of albuminuria and chronic kidney disease (CKD) in individuals with and without diabetes, taking into account the effect of the TBC1D4 variant. The results showed that diabetes was associated with an elevated risk of albuminuria, while the TBC1D4 variant was protective against the development of albuminuria. However, neither diabetes nor the TBC1D4 variant were significantly associated with CKD. The findings suggest a potential renoprotective effect of the TBC1D4 variant on albuminuria, warranting further investigation.