Genetic Variation and Association Analyses of the Nuclear Respiratory Factor 1 (nRF1) Gene in Chinese Patients With Type 2 Diabetes
- Yang Liu1,
- Nifang Niu1,
- Xilin Zhu1,
- Te Du1,
- Xin Wang1,
- Dongmei Chen1,
- Xiaopan Wu1,
- Harvest F. Gu2 and
- Ying Liu1
- 1National 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
- 2Rolf Luft Centre for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
- Address correspondence and reprint requests to Ying Liu, PhD, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 5 Dongdan 3 Tiao, Beijing 100005, China. E-mail: liuyingpumc{at}yahoo.com
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 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.
- HWE, Hardy-Weinberg equilibrium
- MAF, minor allele frequency
- NRF1, nuclear respiratory factor 1
- OHA, oral hypoglycemic agent
- PGC, peroxisome proliferator–activated receptor γ coactivator
- PPARγ, peroxisome proliferator–activated receptor γ
- RFLP, restriction fragment–length polymorphism
- SNP, single nucleotide polymorphism
- UTR, untranslated region
Footnotes
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Published ahead of print at http://diabetes.diabetesjournals.org on December 2007. DOI: 10.2337/db07-0008.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-0008.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received January 3, 2007.
- Accepted November 21, 2007.
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