Genetic Variation and Association Analyses of the Nuclear Respiratory Factor 1 (NRF1) Gene in Chinese Patients with Type 2 Diabetes

Abstract

Objective: Nuclear respiratory factor 1 (NRF1) is a strong biological and positional candidate to contribute to type 2 diabetes susceptibility. This study aimed at evaluating associations between NRF1 genetic polymorphisms and development of type 2 diabetes.

Research Design and Methods: Using a variation screening approach, 6 novel and 10 known single nucleotide polymorphisms (SNPs) in the NRF1 gene were identified. Nine SNPs were then selected using pairwise tagging with an r² cutoff of 0.8 and/or minor allele frequency (MAF) of >5%, and genotyped in 596 type 2 diabetes patients and 431 non-diabetic subjects, all of which were Han Chinese.

Results: Two novel SNPs (−46127T>C and +98560A>G) were associated with type 2 diabetes (P=0.018 and 0.036; OR for possession of minor allele=0.620 and 3.199, with dominant model and correction for multiple comparisons). In SNP rs1882094 (+141G>T), the non-diabetic controls carrying GG genotype had lower fasting plasma glucose levels than carriers with other genotypes (P=0.0002). One common haplotype (H2) mainly composed of SNPs rs6969098 (−24833 A>G), rs1882094 and another novel variant (+97884G>A) was significantly associated with type 2 diabetes (P=0.016, OR=0.706). Subjects with this haplotype had lower fasting triglyceride levels when compared to those with other haplotypes (P=0.010).

Conclusions: The present study shows an association of SNPs in the NRF1 gene with type 2 diabetes in a Han Chinese population. NRF1 genetic polymorphisms may be a suspectibility factor for type 2 diabetes by conferring abnormalities in triglyceride metabolism. Further studies should replicate this finding using larger and racially diverse populations. (248 words)