Kedenko, Lyudmyla and Lamina, Claudia and Kiesslich, Tobias and Kapur, Karen and Bergmann, Sven and Waterworth, Dawn and Heid, Iris M. and Wichmann, H. -Erich and Kedenko, Igor and Kronenberg, Florian and Paulweber, Bernhard (2012) Genetic Polymorphisms of the Main Transcription Factors for Adiponectin Gene Promoter in Regulation of Adiponectin Levels: Association Analysis in Three European Cohorts. PLOS ONE, 7 (12): e52497. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Adiponectin serum concentrations are an important biomarker in cardiovascular epidemiology with heritability etimates of 30-70%. However, known genetic variants in the adiponectin gene locus (ADIPOQ) account for only 2%-8% of its variance. As transcription factors are thought to play an under-acknowledged role in carrying functional variants, we hypothesized that genetic polymorphisms in genes coding for the main transcription factors for the ADIPOQ promoter influence adiponectin levels. Single nucleotide polymorphisms (SNPs) at these genes were selected based on the haplotype block structure and previously published evidence to be associated with adiponectin levels. We performed association analyses of the 24 selected SNPs at forkhead box O1 (FOXO1), sterol-regulatory-element-binding transcription factor 1 (SREBF1), sirtuin 1 (SIRT1), peroxisome-proliferator-activated receptor gamma (PPARG) and transcription factor activating enhancer binding protein 2 beta (TFAP2B) gene loci with adiponectin levels in three different European cohorts: SAPHIR (n = 1742), KORA F3 (n = 1636) and CoLaus (n = 5355). In each study population, the association of SNPs with adiponectin levels on log-scale was tested using linear regression adjusted for age, sex and body mass index, applying both an additive and a recessive genetic model. A pooled effect size was obtained by meta-analysis assuming a fixed effects model. We applied a significance threshold of 0.0033 accounting for the multiple testing situation. A significant association was only found for variants within SREBF1 applying an additive genetic model (smallest p-value for rs1889018 on log(adiponectin) = 0.002, beta on original scale = -0.217 mu g/ml), explaining similar to 0.4% of variation of adiponectin levels. Recessive genetic models or haplotype analyses of the FOXO1, SREBF1, SIRT1, TFAPB2B genes or sex-stratified analyses did not reveal additional information on the regulation of adiponectin levels. The role of genetic variations at the SREBF1 gene in regulating adiponectin needs further investigation by functional studies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES-MELLITUS; ACTIVATED-RECEPTOR-GAMMA; PLASMA ADIPONECTIN; METABOLIC SYNDROME; PRO12ALA POLYMORPHISM; SERUM ADIPONECTIN; ADIPOSE-TISSUE; JAPANESE POPULATION; PPAR-GAMMA-2 GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Apr 2020 13:22 |
| Last Modified: | 30 Apr 2020 13:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17581 |
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