Background: Diabetic nephropathy is the most common cause of chronic kidney disease in the developed countries. Clinical characteristics do not fully predict development of diabetic nephropathy in diabetic patients. There have been few genome-wide association studies (GWAS).
Methods: We conducted a GWAS to identify common genetic variations that affected renal function in a Japanese population of 1,117 patients with type 2 diabetes mellitus (T2D) extracted from 14,091 participants appropriate for GWAS as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Genotyping was performed at a central laboratory using a HumanOmniExpressExome-8 v1.2 BeadChip array. Genotype imputation was performed using SHAPEIT and Minimac3 software based on the 1000 Genomes reference panel (phase 3). Estimated glomerular filtration rate (eGFR) was calculated according to Matsuo et al. for each patient. The association for the imputed variants with eGFR was performed by a linear regression analysis adjusted for age and sex.
Results: We found that rs869312667 at NBEA (β=1.23, P=1.03E-08) and rs8523 at ELOVL2 (β=24.4, P=1.64E-08) were significantly associated with eGFR. These genes have been reported to participate in several metabolic functions and were associated with some disease conditions. However, no previous reports have implied that these genes were related to diabetic nephropathy.
Conclusions: rs869312667 at NBEA and rs8523 at ELOVL2 were significantly associated with eGFR in patients with T2D in Japanese.