Journal of Molecular Medicine

, Volume 84, Issue 2, pp 112–121

Human genetics of adiponectin in the metabolic syndrome

Review

Abstract

Adiponectin, an adipose-derived plasma protein, has been well established to be an important biomarker for metabolic syndrome and its complications after exhausted studies in humans. Animal and cell culture experiments also support most claims from human observations of its roles in the metabolic syndrome. Reproducible results of human genetic studies of diverse ethnic origin and by different investigators may provide the evidence for its causative roles in the pathogenesis of the metabolic syndrome and further insight into the genetic constitutions of the metabolic syndrome. Some of the common polymorphisms in the promoter region, exon and intron 2, and the rare nonsynonymous mutations in exon 3 of the human adiponectin gene were repeatedly shown in many studies from many different ethnic populations to associate with the phenotypes related to body weight, glucose metabolism, insulin sensitivity, and risk of type 2 diabetes mellitus and coronary artery disease. The association of adiponectin genetic variations with dyslipidemia and blood pressure was less explored. The common polymorphisms and rare mutations of the human adiponectin gene itself were demonstrated to associate with differential expression of adiponectin at the plasma protein level and mRNA level in adipose tissue. The PPARγ2 Pro12Ala variants were also shown to influence insulin sensitivity in interaction with adiponectin genotype or to influence plasma adiponectin levels. However, the results were not consistent. Three genome-wide scans for the loci that regulate plasma adiponectin concentration suggest further exploration on chromosomes 5, 9, 14, 15, and 18 is required. These human genetic studies on adiponectin and the metabolic syndrome strongly suggest that adiponectin is one of the causative factors in its pathogenesis and provide significant insights into the genetic makeup of the metabolic syndrome. Extension from these studies may accelerate the discovery of new molecular targets for future therapeutic interventions.

Keywords

Adiponectin Genetic variants Metabolic syndrome Genetics Pharmacogenetics 

Abbreviations

MetS

Metabolic syndrome

HIV

Human immunodeficiency virus

CAD

Coronary artery disease

PCOS

Polycystic ovary syndrome

T2DM

Type 2 diabetes mellitus

IGT

Impaired glucose tolerance

AUC

Area under curve

OGTT

Oral glucose tolerance test

PPARγ

Peroxisome proliferator-activated receptor gamma

HOMA

Homeostasis model assessment

HDL

High-density lipoprotein

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan UniversityTaipeiTaiwan,People's Republic of China
  2. 2.Division of Endocrinology and Metabolism, Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan,People's Republic of China
  3. 3.Institute of Biomedical SciencesAcademia SinicaTaipeiTaiwan,People's Republic of China

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