Association between polymorphisms in the nuclear respiratory factor 1 gene and type 2 diabetes mellitus in the Korean population

Aims/hypothesis: Dysfunction in mitochondrial oxidative phosphorylation plays a central role in insulin resistance and type 2 diabetes. Nuclear respiratory factor 1 (NRF1) is a transcription factor that acts on nuclear genes encoding respiratory subunits and components of the mitochondrial transcription and replication machinery. Thus, we investigated its genetic association with type 2 diabetes. Methods: The NRF1 gene was sequenced to identify polymorphisms in 24 Korean DNA samples and then common variants were genotyped in 766 patients with type 2 diabetes and 303 non-diabetic subjects. Results: Twelve single nucleotide polymorphisms and one insertion/deletion polymorphism were identified. Six common variants among them were genotyped in a larger study. Although three individual polymorphisms appeared to be associated with type 2 diabetes (g.-46350insdel A, g.+141G > T and g.+54529A > G), the effects were only marginal. However, a haplotype (H2) was associated with a decreased risk of type 2 diabetes and another haplotype (H4) was associated with an increased risk of type 2 diabetes (p values for the Haplo.Score test were 0.009 and 0.004, respectively). Conclusions/interpretation: We demonstrated that two common haplotypes of NRF1 gene are associated with type 2 diabetes in the Korean population.