Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the women's health initiative observational study

Yi Hsiang Hsu, Tianhua Niu, Yiqing Song, Lesley Tinker, Lewis H. Kuller, Simin Liu

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1101-1107
Number of pages7
JournalDiabetes
Volume57
Issue number4
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

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Women's Health
Multigene Family
Haplotypes
Observational Studies
Type 2 Diabetes Mellitus
Hispanic Americans
Single Nucleotide Polymorphism
Intergenic DNA
Asian Americans
African Americans
Case-Control Studies
Homeostasis
Research Design
Chromosomes
Odds Ratio
Body Weight
Prospective Studies
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the women's health initiative observational study. / Hsu, Yi Hsiang; Niu, Tianhua; Song, Yiqing; Tinker, Lesley; Kuller, Lewis H.; Liu, Simin.

In: Diabetes, Vol. 57, No. 4, 01.04.2008, p. 1101-1107.

Research output: Contribution to journalArticle

Hsu, Yi Hsiang ; Niu, Tianhua ; Song, Yiqing ; Tinker, Lesley ; Kuller, Lewis H. ; Liu, Simin. / Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the women's health initiative observational study. In: Diabetes. 2008 ; Vol. 57, No. 4. pp. 1101-1107.
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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.",
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AU - Kuller, Lewis H.

AU - Liu, Simin

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