title: The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians.
abstract: Low concentrations of adiponectin, the protein product of the APM1 gene, have been reported to be associated with obesity and insulin resistance. However, contrasting results have been described on the genetic variability in APM1 and characteristics of the metabolic syndrome and adiponectin serum concentrations. In the present study, we investigated the association of the two most well-known SNPs of APM1 (+45T>G and +276G>T) and their haplotypes, with serum adiponectin concentrations, metabolic parameters and intima-media thickness of the carotid arteries in 1,745 well-phenotyped asymptomatic unrelated Caucasian subjects of the SAPHIR cohort. The common T-allele (88.5%) of SNP +45T>G and the common G-allele (70.5%) of SNP +276G>T were associated with significantly lower serum adiponectin levels (P = 0.0008 and P = 0.00005, respectively). The most frequent haplotype TG (59.0%) defined by both loci showed a strong association with lower serum adiponectin concentrations (P = 0.000000002). A clear effect per copy of the respective haplotype was observed. This association was most pronounced in lean and insulin-sensitive subjects. The two less common haplotypes TT (29.5%) and GG (11.5%) were associated with higher serum adiponectin levels in a dose-dependent association. Interestingly, no significant association between the adiponectin 45-276 haplotypes and the majority of parameters of the metabolic syndrome or intima-media thickness of the carotid arteries was found in our study. In summary, we replicated a strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy Caucasians. However, we could not confirm an association of this gene locus with metabolic parameters of the insulin resistance syndrome.
authors.affiliation: First Department of Internal Medicine, St. Johann Spital, Paracelsus Private Medical University Salzburg, Austriaia.
authors.forename: Vitolds
authors.initials: V
authors.lastname: Mackevics
authors.forename: Iris M
authors.initials: IM
authors.lastname: Heid
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Wagner
authors.forename: Paula
authors.initials: P
authors.lastname: Cip
authors.forename: Hildegard
authors.initials: H
authors.lastname: Doppelmayr
authors.forename: Aivars
authors.initials: A
authors.lastname: Lejnieks
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Günther
authors.initials: G
authors.lastname: Ladurner
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Bernhard
authors.initials: B
authors.lastname: Iglseder
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001794:Blood Pressure; D002339:Carotid Arteries / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D052242:Adiponectin; D007328:Insulin