A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2with serum creatinine level

Title: A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2with serum creatinine level
Authors: Pattaro, C
De Grandi, A
Vitart, V
Hayward, C
Franke, A
Aulchenko, YS
Johansson, A
Wild, SH
Melville, SA
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, BA
Riegler, P
Minelli, C
Wright, AF
Campbell, H
Van Duijn, CM
Gyllensten, U
Wilson, JF
Krawczak, M
Rudan, I
Pramstaller, PP
EUROSPAN consortium
Item Type: Journal Article
Abstract: 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.
Issue Date: 11-Mar-2010
Date of Acceptance: 11-Mar-2010
ISSN: 1471-2350
Publisher: BioMed Central
Journal / Book Title: BMC Medical Genetics
Volume: 11
Copyright Statement: © Pattaro et al. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Adolescent
Aged, 80 and over
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 8
Cohort Studies
European Continental Ancestry Group
Genome-Wide Association Study
Middle Aged
Non-Fibrillar Collagens
Polymorphism, Single Nucleotide
Receptors, GABA-A
Reproducibility of Results
Synaptotagmin I
Young Adult
EUROSPAN consortium
Genetics & Heredity
0604 Genetics
1103 Clinical Sciences
Publication Status: Published
Article Number: 41
Appears in Collections:Infectious Disease Epidemiology
National Heart and Lung Institute
Faculty of Medicine

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