Human genetics of adiponectin in the metabolic syndrome
Journal
Journal of Molecular Medicine
Journal Volume
84
Journal Issue
2
Pages
112-121
Date Issued
2006
Author(s)
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 non-synonymous 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. ? Springer-Verlag 2005.
SDGs
Other Subjects
acarbose; adenovirus vector; adiponectin; angiotensin 2 receptor antagonist; antihypertensive agent; dipeptidyl carboxypeptidase inhibitor; glimepiride; messenger RNA; metformin; peroxisome proliferator activated receptor gamma agonist; pioglitazone; plasma protein; recombinant adiponectin; recombinant protein; sulfonylurea; unclassified drug; adipose tissue; atherosclerosis; blood level; blood pressure; body weight; cell culture; chromosome 14; chromosome 15; chromosome 18; chromosome 5; chromosome 9; coronary artery disease; dyslipidemia; ethnic group; exon; gene mutation; gene structure; gene therapy; genetic polymorphism; genetic variability; glucose metabolism; human; human genetics; hyperglycemia; hypotension; insulin resistance; insulin sensitivity; intron; kidney disease; lipid metabolism; lipodystrophy; metabolic disorder; metabolic syndrome X; molecular mechanics; non insulin dependent diabetes mellitus; nonhuman; nucleotide sequence; obesity; pathogenesis; phenotypic variation; promoter region; protein expression; protein protein interaction; restenosis; review; risk factor; virus carrier; Adiponectin; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; Metabolic Syndrome X; Obesity; Polymorphism, Genetic
Type
review