Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the women's health initiative observational study

Kei Hang K Chan, Yiqing Song, Yi Hsiang Hsu, Nai Chieh Y You, Lesley F. Tinker, Simin Liu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Adipocypte fatty acid-binding protein-4 (FABP4/adipocyte P2) may play a central role in energy metabolism and inflammation. In animal models, defects of the aP2 gene (aP2-/-) partially protected against the development of obesity-related insulin resistance, dyslipidemia, and atherosclerosis. However, it is unclear whether common genetic variation in FABP4 gene contributes to risk of type 2 diabetes (T2D) or diabetes-related metabolic traits in humans. We comprehensively assess the genetic associations of variants in the FABP4 gene with T2D risk and diabetes-associated biomarkers in a prospective study of 1,529 cases and 2,147 controls among postmenopausal women aged 50-79 years who enrolled in the Women's Health Initiative Observational Study (WHI-OS). We selected and genotyped a total of 11 haplotype-tagging single-nucleotide polymorphisms (tSNPs) spanning 41.3kb across FABP4 in all samples. None of the SNPs and their derived haplotypes showed significant association with T2D risk. There were no significant associations between SNPs and plasma levels of inflammatory and endothelial biomarkers, including C-reactive protein, tumor necrosis factor (TNF), interleukin-6 (IL-6), E-selectin, and intercellular adhesion molecule (ICAM-1). Among African-American women, several SNPs were significantly associated with lower levels of vascular cell adhesion molecule-1 (VCAM-1), especially among those with incident T2D. On average, plasma levels of VCAM-1 were significantly lower among carriers of each minor allele at rs1486004(C/T; 1.08ng/ml, P = 0.01), rs7017115(A/G; 1.07ng/ml, P = 0.02), and rs2290201(C/T; 1.12ng/ml, P = 0.002) as compared with the homozygotes of the common allele, respectively. After adjusting for multiple testing, carriers of the rs2290201 minor allele remained significantly associated with decreasing levels of plasma VCAM-1 in these women (P = 0.02). In conclusion, our finding from a multiethnic cohort of postmenopausal women did not support the notion that common genetic variants in the FABP4 gene may trigger increased risk of T2D. The observed significant association between reduced VCAM-1 levels and FABP4 genotypes in African-American women warrant further confirmation.

Original languageEnglish (US)
Pages (from-to)1812-1820
Number of pages9
JournalObesity
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

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Fatty Acid-Binding Proteins
Women's Health
Observational Studies
Vascular Cell Adhesion Molecule-1
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
Alleles
Intercellular Adhesion Molecule-1
African Americans
Haplotypes
Genes
Biomarkers
E-Selectin
Homozygote
Dyslipidemias
Plasma Cells
Adipocytes
C-Reactive Protein
Energy Metabolism
Insulin Resistance

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the women's health initiative observational study. / Chan, Kei Hang K; Song, Yiqing; Hsu, Yi Hsiang; You, Nai Chieh Y; F. Tinker, Lesley; Liu, Simin.

In: Obesity, Vol. 18, No. 9, 01.09.2010, p. 1812-1820.

Research output: Contribution to journalArticle

Chan, Kei Hang K ; Song, Yiqing ; Hsu, Yi Hsiang ; You, Nai Chieh Y ; F. Tinker, Lesley ; Liu, Simin. / Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the women's health initiative observational study. In: Obesity. 2010 ; Vol. 18, No. 9. pp. 1812-1820.
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