Kaess, Bernhard M. and Barnes, Timothy A. and Stark, Klaus and Charchar, Fadi J. and Waterworth, Dawn and Song, Kijoung and Wang, William Y. S. and Vollenweider, Peter and Waeber, Gerard and Mooser, Vincent and Zukowska-Szczechowska, Ewa and Samani, Nilesh J. and Hengstenberg, Christian and Tomaszewski, Maciej (2010) FGF21 signalling pathway and metabolic traits - genetic association analysis. EUROPEAN JOURNAL OF HUMAN GENETICS, 18 (12). pp. 1344-1348. ISSN 1018-4813,
Full text not available from this repository. (Request a copy)Abstract
Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol-LDL-C, HDL-cholesterol-HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q<0.5. Of these, only one FGFR2 polymorphism (rs2071616) showed replicated association with LDL-C in both CoLaus (P=0.009) and men from GerMIFS (P=0.017). The direction of allelic effect of rs2071616 upon LDL-C was consistent in all examined populations. These data show that common genetic variations in FGFR2 may be associated with LDL-C in subjects of white European ancestry. European Journal of Human Genetics (2010) 18, 1344-1348; doi: 10.1038/ejhg.2010.130; published online 18 August 2010
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CORONARY-ARTERY-DISEASE; BETA-KLOTHO; PPAR-ALPHA; FIBROBLAST-GROWTH-FACTOR-21; HYPERTENSION; GENOMEWIDE; EXPRESSION; LINKAGE; FGF-21; FAMILY; fibroblast growth factor 21; fibroblast growth factor receptor 2; cholesterol; single-nucleotide polymorphism; genome-wide association studies |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2020 07:33 |
| Last Modified: | 06 Jul 2020 07:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/23783 |
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