PMID- 18755175
OWN - NLM
STAT- MEDLINE
DCOM- 20090121
LR  - 20161124
IS  - 0009-8981 (Print)
IS  - 0009-8981 (Linking)
VI  - 398
IP  - 1-2
DP  - 2008 Dec
TI  - Associations between polymorphisms in the mitochondrial uncoupling proteins 
      (UCPs) with T2DM.
PG  - 27-33
LID - 10.1016/j.cca.2008.07.029 [doi]
AB  - 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.
FAU - Lee, Hye-Ja
AU  - Lee HJ
AD  - Division of Metabolic Disease, Center for Biomedical Sciences, National Institute 
      of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea.
FAU - Ryu, Ha-Jung
AU  - Ryu HJ
FAU - Shin, Hyoung-Doo
AU  - Shin HD
FAU - Park, Byung Lae
AU  - Park BL
FAU - Kim, Jong Yeol
AU  - Kim JY
FAU - Cho, Young Min
AU  - Cho YM
FAU - Park, Kyong Soo
AU  - Park KS
FAU - Song, Jihyun
AU  - Song J
FAU - Oh, Bermseok
AU  - Oh B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080805
PL  - Netherlands
TA  - Clin Chim Acta
JT  - Clinica chimica acta; international journal of clinical chemistry
JID - 1302422
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Uncoupling Protein 1)
SB  - IM
MH  - 3' Flanking Region
MH  - 5' Flanking Region
MH  - Aged
MH  - Diabetes Mellitus, Type 2/epidemiology/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Fluorescence Polarization Immunoassay
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Introns/genetics
MH  - Ion Channels/*genetics
MH  - Korea/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Mitochondrial Proteins/*genetics
MH  - Odds Ratio
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide
MH  - Uncoupling Protein 1
EDAT- 2008/08/30 09:00
MHDA- 2009/01/22 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/04/21 00:00 [received]
PHST- 2008/06/27 00:00 [revised]
PHST- 2008/07/31 00:00 [accepted]
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2009/01/22 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - S0009-8981(08)00384-7 [pii]
AID - 10.1016/j.cca.2008.07.029 [doi]
PST - ppublish
SO  - Clin Chim Acta. 2008 Dec;398(1-2):27-33. doi: 10.1016/j.cca.2008.07.029. Epub 
      2008 Aug 5.