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

• Published in: International Journal of Circumpolar Health
• Main Authors: Overvad, Maria, Díaz, Lars Jorge, Bjerregaard, Peter, Pedersen, Michael Lynge, Larsen, Christina Viskum Lytken, Grarup, Niels, Hansen, Torben, Rossing, Peter, Jørgensen, Marit Eika
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2023
• Subjects: CKD; complications; diabetes; genetics; Greenland; Circumpolar Health; greenlander*; International Journal of Circumpolar Health; inuit
• Online Access: https://curis.ku.dk/portal/da/publications/the-effect-of-diabetes-and-the-diabetogenic-tbc1d4-parg684ter-variant-on-kidney-function-in-inuit-in-greenland(54863bd2-c9e7-4c32-b44d-22b1e1a0cd20).html; https://doi.org/10.1080/22423982.2023.2191406; https://curis.ku.dk/ws/files/342506497/The_effect_of_diabetes_and_the_diabetogenic_TBC1D4_p_Arg684ter_variant_on_kidney_function_in_Inuit_in_Greenland.pdf

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.