C.CHAN1, R.GURUNG1, K.ANG1, S.C.LIM1
Khoo Teck Puat Hospital1
Type 2 diabetes (T2D) is a complex metabolic disease and increases the risk for kidney failure. Mitochondrial haplogroups, which are patterns of single nucleotide polymorphisms (SNPs) in the mtDNA have been found to play a role in metabolic dysregulation and diabetic complications. In this study, we aim to determine whether mitochondrial haplogroup N9a is associated with annual decline in estimated glomerular filtration rate (eGFR) in T2D patients.
520 Chinese T2D patients without chronic kidney disease (eGFR ≥60ml/min/1.73m² at baseline) and followed for mean of 5.64 years were included in this study. Annual decline in eGFR was determined using Linear Mixed models. Mitochondrial haplogroup N9a is identified through Genotyping of three SNPs: 5231A, 12358G and 12372A. Multivariate linear regression model was fitted to determine the relationship between haplogroup and annual eGFR decline rate.
Among 520 patients with mean [SD] age of 56 , 274 (53%) male, 21 (4%) had the N9a haplogroup. The annual decline rate was significantly greater in N9a patients compared to non-N9a (-3.12 vs -1.97 mL/min/1.73m2/year, P=0.039). In a multivariate model adjusted for age, sex, body mass index, systolic blood pressure, diabetes duration, HBA1c, eGFR, uACR and intake of RAS antagonist and insulin, patients with N9a showed significantly greater decrease in eGFR per year (1.014 mL/min/1,73m2, P=0.045) compared to non-N9a.
In T2D patients without CKD, haplogroup N9a is independently associated with higher risk for future decline in kidney function. N9a can therefore be used as a biomarker to stratify for those at high risk of early kidney complications.