title: 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.
  
  
  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 r(2) cutoff of 0.8 and/or minor allele frequency of >5% and genotyped in 596 type 2 diabetic patients and 431 nondiabetic subjects, all of whom were Han Chinese.
  
  
  RESULTS
  Two novel SNPs (-46127T>C and +98560A>G) were associated with type 2 diabetes (P = 0.018 and 0.036; for possession of minor allele, odds ratio [OR] 0.620 and 3.199, with dominant model and correction for multiple comparisons). In SNP rs1882094 (+141G>T), the nondiabetic control subjects 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 with 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.
authors: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. liuyingpumc@yahoo.com
authors: Yang
authors: Y
authors: Liu
authors: Nifang
authors: N
authors: Niu
authors: Xilin
authors: X
authors: Zhu
authors: Te
authors: T
authors: Du
authors: Xin
authors: X
authors: Wang
authors: Dongmei
authors: D
authors: Chen
authors: Xiaopan
authors: X
authors: Wu
authors: Harvest F
authors: HF
authors: Gu
authors: Ying
authors: Y
authors: Liu
mesh_terms: D000368:Aged; D044466:Asian People; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics*; D016017:Odds Ratio
chemical_list: C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1