TCF7L2 variants associate with CKD progression and renal function in population-based cohorts.

Area of Science:

• Genetics
• Nephrology
• Metabolic Diseases

Background:

• Genetic variants influencing diabetes susceptibility may also impact kidney disease.
• The role of transcription factor 7-like 2 (TCF7L2) gene variants in chronic kidney disease (CKD) progression and kidney function markers remains unclear.

Purpose of the Study:

• To investigate the association between known diabetes-associated TCF7L2 gene variants and CKD progression and kidney function markers.

Main Methods:

• Genotyping of common TCF7L2 variants (rs7903146, rs7901695) in three large population-based cohorts: Atherosclerosis Risk in Communities Study (ARIC), Framingham Heart Offspring Cohort (FHS), and Heredity and Phenotype Intervention Heart Study (HAPI).
• Statistical analyses, including hazard ratios and adjusted models, were used to assess associations with CKD progression, estimated glomerular filtration rate (eGFR), cystatin C, and albuminuria.

Main Results:

• Diabetes-risk alleles in TCF7L2 (rs7903146 and rs7901695) were significantly associated with CKD progression in ARIC participants, especially those without baseline diabetes.
• In the FHS cohort, the rs7903146 T allele correlated with lower eGFR and higher cystatin C levels.
• The HAPI cohort showed an association between the rs7901695 C allele and reduced eGFR, along with other TCF7L2 variants.
• No significant associations were found between the studied variants and albuminuria in ARIC or FHS cohorts.

Conclusions:

• Population-based studies suggest that TCF7L2 gene variants are associated with impaired kidney function and CKD progression.
• The association appears significant overall and particularly in individuals without diabetes, indicating a potential role for TCF7L2 in kidney health independent of diabetes status.