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Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study.
Diabetes 2008; 57(4):1101-7D

Abstract

OBJECTIVE

Mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to type 2 diabetes risk in a prospective, case-control study nested in the Women's Health Initiative Observational Study, an ethnically diverse cohort of postmenopausal women including Caucasian, African, Hispanic, and Asian American subjects. We genotyped 14 tag SNPs in 1,584 incident type 2 diabetes case and 2,198 control subjects matched by age, ethnicity, clinical center, time of blood draw, and length of follow-up.

RESULTS

We identified a haplotype set (rs591758-rs668514- rs647126-rs1800006, spanning the UCP2-UCP3 intergenic and UCP3 regions) as significantly associated with greater type 2 diabetes risk (nominal P = 0.0011, permutation P = 0.046) in Caucasian women, especially among overweight Caucasians (BMI >25 kg/m(2)) (nominal P = 0.0006, permutation P = 0.032). Compared with the most common haplotype (h1010 as the referent), haplotype h0001 (19.5% in control subjects) had odds ratios of 2.0 (95% CI 1.13-3.37) in Caucasians and 3.8 (1.44-9.93) in Caucasian overweight women. Similar haplotype-type 2 diabetes association was also observed among Hispanic women who were overweight.

CONCLUSIONS

These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women. These data warrant further confirmation in future prospective and experimental studies.

Authors+Show Affiliations

Institute for Aging Research, Hebrew Senior Life and Harvard Medical School, Boston, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18223008

Citation

Hsu, Yi-Hsiang, et al. "Genetic Variants in the UCP2-UCP3 Gene Cluster and Risk of Diabetes in the Women's Health Initiative Observational Study." Diabetes, vol. 57, no. 4, 2008, pp. 1101-7.
Hsu YH, Niu T, Song Y, et al. Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. Diabetes. 2008;57(4):1101-7.
Hsu, Y. H., Niu, T., Song, Y., Tinker, L., Kuller, L. H., & Liu, S. (2008). Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. Diabetes, 57(4), pp. 1101-7. doi:10.2337/db07-1269.
Hsu YH, et al. Genetic Variants in the UCP2-UCP3 Gene Cluster and Risk of Diabetes in the Women's Health Initiative Observational Study. Diabetes. 2008;57(4):1101-7. PubMed PMID: 18223008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women's Health Initiative Observational Study. AU - Hsu,Yi-Hsiang, AU - Niu,Tianhua, AU - Song,Yiqing, AU - Tinker,Lesley, AU - Kuller,Lewis H, AU - Liu,Simin, Y1 - 2008/01/25/ PY - 2008/1/29/pubmed PY - 2008/4/26/medline PY - 2008/1/29/entrez SP - 1101 EP - 7 JF - Diabetes JO - Diabetes VL - 57 IS - 4 N2 - OBJECTIVE: Mitochondrial uncoupling proteins (UCPs) are involved in body weight regulation and glucose homeostasis. Genetic variants in the UCP2-UCP3 gene cluster, located on chromosome 11q13, may play a significant role in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a comprehensive assessment of common single nucleotide polymorphisms (SNPs) at the 70-kb UCP2-UCP3 gene cluster in relation to type 2 diabetes risk in a prospective, case-control study nested in the Women's Health Initiative Observational Study, an ethnically diverse cohort of postmenopausal women including Caucasian, African, Hispanic, and Asian American subjects. We genotyped 14 tag SNPs in 1,584 incident type 2 diabetes case and 2,198 control subjects matched by age, ethnicity, clinical center, time of blood draw, and length of follow-up. RESULTS: We identified a haplotype set (rs591758-rs668514- rs647126-rs1800006, spanning the UCP2-UCP3 intergenic and UCP3 regions) as significantly associated with greater type 2 diabetes risk (nominal P = 0.0011, permutation P = 0.046) in Caucasian women, especially among overweight Caucasians (BMI >25 kg/m(2)) (nominal P = 0.0006, permutation P = 0.032). Compared with the most common haplotype (h1010 as the referent), haplotype h0001 (19.5% in control subjects) had odds ratios of 2.0 (95% CI 1.13-3.37) in Caucasians and 3.8 (1.44-9.93) in Caucasian overweight women. Similar haplotype-type 2 diabetes association was also observed among Hispanic women who were overweight. CONCLUSIONS: These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women. These data warrant further confirmation in future prospective and experimental studies. SN - 1939-327X UR - https://www.unboundmedicine.com/medline/citation/18223008/Genetic_variants_in_the_UCP2_UCP3_gene_cluster_and_risk_of_diabetes_in_the_Women's_Health_Initiative_Observational_Study_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=18223008 DB - PRIME DP - Unbound Medicine ER -