OP-7：Association between Polymorphisms in the Nuclear Respiratory Factor 1 Gene and Type 2 Diabetes Mellitus in the Korean Population

Young Min Cho,^1,2 Hyoung Doo Shin,³ Hye Seung Jeong^1,2, Min Kyong Moon^1,2, Hak Chul Jang^1,2, Kyong Soo Park,^1,2, and Hong Kyu Lee^1,2

¹Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

²Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea

³Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea

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. Since NRF1 is physiologically linked to glucose metabolism, we investigated its genetic association with type 2 diabetes.

Methods. The NRF1 gene was sequenced to screen polymorphisms using 24 Korean DNA samples and then common variants were genotyped in 766 patients with type 2 diabetes and 303 nondiabetic subjects.

Results.  Twelve single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were identified and 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 (adjusted odds ratio [OR] = 0.555 [0.360 - 0.854], P = 0.007) and another haplotype (H4) was associated with an increased risk of type 2 diabetes (adjusted OR = 1.364 [1.081 - 1.721], P = 0.009).

Conclusions/interpretation. In conclusion, we demonstrated that two common haplotypes of NRF1 gene are associated with type 2 diabetes in the Korean population.