PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Pattaro, C.* ; de Grandi, A.* ; Vitart, V.* ; Hayward, C.* ; Franke, A.* ; Aulchenko, Y.S.* ; Johansson, A.* ; Wild, S.H.* ; Melville, S.A.* ; Isaacs, A.* ; Polasek, O.* ; Ellinghaus, D.* ; Kolcic, I.* ; Nöthlings, U.* ; Zgaga, L.* ; Zemunik, T.* ; Gnewuch, C.* ; Schreiber, S.* ; Campbell, S.* ; Hastie, N.* ; Boban, M.* ; Meitinger, T. ; Oostra, B.A.* ; Riegler, P.* ; Minelli, C.* ; Wright, A.F.* ; Campbell, H.* ; van Duijn, C.M.* ; Gyllensten, U.* ; Wilson, J.F.* ; Krawczak, M.* ; Rudan, I.* ; Pramstaller, P.P.*

A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level.

BMC Med. Genet. 11:41 (2010)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Serum creatinine (S CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S CR level is explicable by genetic factors. METHODS: We performed a meta-analysis of genome-wide association studies of S CR undertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with SCR (candidate loci) were replicated in two additional population-based samples ('replication cohorts'). RESULTS: After the discovery meta-analysis, 29 loci were selected for replication. Association between SCR level and polymorphisms in the collagen type XXII alpha 1 (COL22A1) gene, on chromosome 8, and in the synaptotagmin-1 (SYT1) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 x 10(-6) and 1.7 x 10(-4), respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (GABRR2) gene and the ubiquitin-conjugating enzyme E2-J1 (UBE2J1) gene (replication p value = 3.6 x 10(-3)). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (UMOD) gene and in the schroom family member 3 (SCHROOM3) gene were also replicated. CONCLUSIONS: While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes SYT1 and GABRR2 corroborate previous findings that highlighted a possible role of the neurotransmitters GABAA receptors in the regulation of the glomerular basement membrane and a possible interaction between GABAA receptors and synaptotagmin-I at the podocyte level.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
2.840
0.824
41
41
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; LINKAGE DISEQUILIBRIUM; ISOLATED POPULATION; AFRICAN-AMERICANS; FRAMINGHAM HEART; SOUTH TYROL; TRAITS; ISLAND
Language english
Publication Year 2010
HGF-reported in Year 2010
e-ISSN 1471-2350
Journal BMC Medical Genetics
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 41 Supplement: ,
Publisher BioMed Central Ltd.
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
PubMed ID 20222955
DOI 10.1186/1471-2350-11-41
WOS ID 000276394000001
Scopus ID 77949425860
Erfassungsdatum 2010-06-10
[➜Report correction]