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Human genetics of adiponectin in the metabolic syndrome

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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.

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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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Acknowledgements

W-S.Y. and L-M.C. were supported by grant (NSC-93-2314-B-002-175) and grant (NSC-93-3112-B-002-005), respectively, from the National Science Council of Taiwan.

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Authors and Affiliations

  1. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan,People's Republic of China

    Wei-Shiung Yang & Lee-Ming Chuang

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, 100, Taipei, Taiwan,People's Republic of China

    Wei-Shiung Yang & Lee-Ming Chuang

  3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan,People's Republic of China

    Wei-Shiung Yang

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Yang, WS., Chuang, LM. Human genetics of adiponectin in the metabolic syndrome. J Mol Med 84, 112–121 (2006). https://doi.org/10.1007/s00109-005-0011-7

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