FGF21 signalling pathway and metabolic traits - genetic association analysis

Kaess, Bernhard M., Barnes, Timothy A., Stark, Klaus, Charchar, Fadi J., Waterworth, Dawn, Song, Kijoung, Wang, William Y. S., Vollenweider, Peter, Waeber, Gerard, Mooser, Vincent, Zukowska-Szczechowska, Ewa, Samani, Nilesh J., Hengstenberg, Christian and Tomaszewski, Maciej (2010) FGF21 signalling pathway and metabolic traits - genetic association analysis. European Journal of Human Genetics, 18 12: 1344-1348. doi:10.1038/ejhg.2010.130


Author Kaess, Bernhard M.
Barnes, Timothy A.
Stark, Klaus
Charchar, Fadi J.
Waterworth, Dawn
Song, Kijoung
Wang, William Y. S.
Vollenweider, Peter
Waeber, Gerard
Mooser, Vincent
Zukowska-Szczechowska, Ewa
Samani, Nilesh J.
Hengstenberg, Christian
Tomaszewski, Maciej
Title FGF21 signalling pathway and metabolic traits - genetic association analysis
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
1476-5438
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1038/ejhg.2010.130
Volume 18
Issue 12
Start page 1344
End page 1348
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2011
Language eng
Formatted 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. © 2010 Macmillan Publishers Limited All rights reserved.
Keyword Fibroblast growth factor 21
Fibroblast growth factor receptor 2
Cholesterol
Single-nucleotide polymorphism
Genome-wide association studies
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Sun, 12 Dec 2010, 00:08:56 EST