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Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM
Cited 22 time in
Web of Science
Cited 25 time in Scopus
- Authors
- Issue Date
- 2008-08-30
- Publisher
- Elsevier
- Citation
- Clin Chim Acta. 2008 Dec;398(1-2):27-33. Epub 2008 Aug 5.
- Keywords
- 3' Flanking Region ; 5' Flanking Region ; Aged ; Diabetes Mellitus, Type 2/epidemiology/*genetics ; Exons/genetics ; Female ; Fluorescence Polarization Immunoassay ; Gene Frequency ; Genotype ; Humans ; Introns/genetics ; Ion Channels/*genetics ; Korea/epidemiology ; Male ; Middle Aged ; Mitochondrial Proteins/*genetics ; Odds Ratio ; Phenotype ; Polymorphism, Single Nucleotide
- Abstract
- BACKGROUND: Mitochondrial uncoupling proteins (UCPs) are considered pivotal regulators of energy and glucose homeostasis. We examined the effect of 23 single nucleotide polymorphisms (SNPs) in the UCP genes on type 2 diabetes mellitus (T2DM) and related phenotypes to identify genetic factors that may be involved in susceptibility to T2DM. METHODS: We directly sequenced the coding region, portions of the 5'- and 3'-flanking sequences, and the intron-exon boundaries of the UCP genes from 24 individuals. We genotyped 23 SNPs in 761 unrelated patients with T2DM and 632 unrelated non-diabetic control subjects and investigated their potential involvement in T2DM. RESULTS: We identified association between T2DM and the following 3 SNPs in UCP2: UCP2 -5331G>A (P=0.018, odds ratio (OR)=1.38, 95% CI (confidence interval)=1.06-1.79), UCP2 -3998C>G (P=0.021, OR=1.37, 95% CI=1.05-1.78), and UCP2 +320C>T (P=0.019, OR=0.73, 95% CI=0.57-0.95). There was strong linkage disequilibrium (LD) among these 3 SNPs (r2=0.94-0.97). UCP2 -5331G>A is a regulatory SNP (rSNP), and its association with T2DM was significant among obese or abdominally obese subjects (P=0.017, OR=1.78, 95% CI=1.11-2.85; P=0.004, OR=1.82, 95% CI=1.21-2.74; respectively). UCP3 -2078C>T of UCP3 SNPs was associated with T2DM only among women (P=0.026, OR=0.71, 95% CI=0.52-0.96). Patients with combinations of the rSNPs UCP2 -5331G>A and UCP3 -2078C>T displayed an increased risk for T2DM. Specifically, those patients homozygous for both rSNPs among susceptible alleles had a higher risk for T2DM than patients heterozygous for one rSNP and homozygous for the other rSNP (P=0.033, OR=1.38, 95% CI=1.03-1.85). This association was more obvious in women (P=0.022, OR=1.58, 95% CI=1.07-2.34). CONCLUSIONS: Our results suggest that the UCP2 -5331G>A and UCP3 -2078C>T polymorphisms are susceptibility markers for T2DM among Koreans.
- ISSN
- 0009-8981 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18755175
http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T57-4T4XRD0-2-8&_cdi=4995&_user=168665&_orig=search&_coverDate=12%2F31%2F2008&_sk=996019998&view=c&wchp=dGLbVzb-zSkzS&md5=f05b4e38f9f79e4d6c6f71acbc64d81c&ie=/sdarticle.pdf
https://hdl.handle.net/10371/46578
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