title: Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians.
abstract: The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Wagner
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Bernhard
authors.initials: B
authors.lastname: Iglseder
authors.forename: Jakob C
authors.initials: JC
authors.lastname: Mueller
authors.forename: Paula
authors.initials: P
authors.lastname: Cip
authors.forename: Günther
authors.initials: G
authors.lastname: Ladurner
authors.forename: Raphael
authors.initials: R
authors.lastname: Reiter
authors.forename: Andreas
authors.initials: A
authors.lastname: Stadlmayr
authors.forename: Vitolds
authors.initials: V
authors.lastname: Mackevics
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006262:Health; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin