Association of Adiponectin Gene Variations with Risk of Incident Myocardial Infarction and Ischemic Stroke: A Nested Case-Control Study (Molecular Diagnostics and Genetics‪)‬

Adiponectin, an adipose tissue-specific plasma protein, is structurally homologous to collagens VIII and X and complement factor C1q (1) and plays an important role in regulating energy homeostasis, glucose and lipid metabolism, and antiinflammatory responses in the vascular system (2-4). Low plasma concentrations of adiponectin have been associated with type 2 diabetes (5), obesity (5), hypertension (6), myocardial infarction (MI) [3] (7), and ischemic stroke (8). Potential mechanisms of adiponectin and its associations with these inflammatory-related diseases include its inhibition of smooth muscle cell proliferation, monocyte adhesion to endothelium, and macrophage uptake by LDL (8). Recent evidence from linkage studies has implicated a region encompassing the adiponectin, C1Q, and collagen domain-containing gene (ADIPOQ, 3827, Gene ID 9370) [4] with risk of coronary heart disease (9) and metabolic syndrome (10). ADIPOQ gene variations have also been shown to be associated with adiponectin plasma concentrations (11-18). Further more, recent studies found an association of selected ADIPOQ gene variants (19), in particular the +276GT (intron2, rs1501299) variation, with decreased cardiovascular risk in patients with (14,20) and without (21) diabetes under a recessive mode of inheritance. To validate and confirm these findings in a prospective setting, we conducted an extended investigation to examine the possible association of 5 variations [-11377CG (rs266729), -10066GA (rsl82052), -3971AG (rs822396), +45TG (rs2241766), and +276GT (rs1501299)] in ADIPOQ with risk of incident MI and ischemic stroke in participants drawn from the Physicians Health Study (PHS) cohort. These variations were selected on the basis of prior evidence of associations with cardiovascular risk, validated allele frequency and heterozygosity, and sequence-demonstrated allelic variation listed in the National Center for Biotechnology Information database (http: / /www.ncbi.nhn.nih.gov).