Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians

被引:176
|
作者
Heid, IM
Wagner, SA
Gohlke, H
Iglseder, B
Mueller, JC
Cip, P
Ladurner, G
Reiter, R
Stadlmayr, A
Mackevics, V
Illig, T
Kronenberg, F
Paulweber, B
机构
[1] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria
[2] GSF Natl Res Ctr Environm & Hlth, Inst Epidemiol, Neuherberg, Germany
[3] Univ Munich, Dept Epidemiol, Munich, Germany
[4] Paracelsus Private Med Univ Salzburg, St Johann Spital, Dept Internal Med 1, Salzburg, Austria
[5] Paracelsus Private Med Univ Salzburg, Dept Neurol, Salzburg, Austria
[6] Tech Univ Munich, Clin Rechts Isar, Inst Med Stat & Epidemiol, D-8000 Munich, Germany
[7] Tech Univ Munich, Clin Rechts Isar, Inst Psychiat & Psychotherapy, D-8000 Munich, Germany
关键词
D O I
10.2337/diabetes.55.02.06.db05-0747
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:375 / 384
页数:10
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