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Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM.
Clin Chim Acta 2008; 398(1-2):27-33CC

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.

Authors+Show Affiliations

Division of Metabolic Disease, Center for Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, Eunpyung-gu, Seoul, 122-701, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18755175

Citation

Lee, Hye-Ja, et al. "Associations Between Polymorphisms in the Mitochondrial Uncoupling Proteins (UCPs) With T2DM." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 398, no. 1-2, 2008, pp. 27-33.
Lee HJ, Ryu HJ, Shin HD, et al. Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM. Clin Chim Acta. 2008;398(1-2):27-33.
Lee, H. J., Ryu, H. J., Shin, H. D., Park, B. L., Kim, J. Y., Cho, Y. M., ... Oh, B. (2008). Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM. Clinica Chimica Acta; International Journal of Clinical Chemistry, 398(1-2), pp. 27-33. doi:10.1016/j.cca.2008.07.029.
Lee HJ, et al. Associations Between Polymorphisms in the Mitochondrial Uncoupling Proteins (UCPs) With T2DM. Clin Chim Acta. 2008;398(1-2):27-33. PubMed PMID: 18755175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM. AU - Lee,Hye-Ja, AU - Ryu,Ha-Jung, AU - Shin,Hyoung-Doo, AU - Park,Byung Lae, AU - Kim,Jong Yeol, AU - Cho,Young Min, AU - Park,Kyong Soo, AU - Song,Jihyun, AU - Oh,Bermseok, Y1 - 2008/08/05/ PY - 2008/04/21/received PY - 2008/06/27/revised PY - 2008/07/31/accepted PY - 2008/8/30/pubmed PY - 2009/1/22/medline PY - 2008/8/30/entrez SP - 27 EP - 33 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin. Chim. Acta VL - 398 IS - 1-2 N2 - 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. SN - 0009-8981 UR - https://www.unboundmedicine.com/medline/citation/18755175/Associations_between_polymorphisms_in_the_mitochondrial_uncoupling_proteins__UCPs__with_T2DM_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(08)00384-7 DB - PRIME DP - Unbound Medicine ER -