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

• Main Authors: Oostra Ben A, Meitinger Thomas, Boban Mladen, Hastie Nick, Campbell Susan, Schreiber Stefan, Gnewuch Carsten, Zemunik Tatijana, Zgaga Lina, Nöthlings Ute, Kolcic Ivana, Ellinghaus David, Polasek Ozren, Isaacs Aaron, Melville Scott A, Wild Sarah H, Johansson Asa, Aulchenko Yurii S, Franke Andre, Hayward Caroline, Vitart Veronique, De Grandi Alessandro, Pattaro Cristian, Riegler Peter, Minelli Cosetta, Wright Alan F, Campbell Harry, van Duijn Cornelia M, Gyllensten Ulf, Wilson James F, Krawczak Michael, Rudan Igor, Pramstaller Peter P
• Format: Article
• Language: English
• Published: BMC 2010-03-01
• Series: BMC Medical Genetics
• Online Access: http://www.biomedcentral.com/1471-2350/11/41
• ISSN: 1471-2350

<p>Abstract</p> <p>Background</p> <p>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_CRlevel is explicable by genetic factors.</p> <p>Methods</p> <p>We performed a meta-analysis of genome-wide association studies of S_CRundertaken 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 S_CR(candidate loci) were replicated in two additional population-based samples ('replication cohorts').</p> <p>Results</p> <p>After the discovery meta-analysis, 29 loci were selected for replication. Association between S_CRlevel and polymorphisms in the collagen type XXII alpha 1 (<it>COL22A1</it>) gene, on chromosome 8, and in the synaptotagmin-1 (<it>SYT1</it>) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10^-6and 1.7 × 10^-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (<it>GABRR2</it>) gene and the ubiquitin-conjugating enzyme E2-J1 (<it>UBE2J1</it>) gene (replication p value = 3.6 × 10^-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (<it>UMOD</it>) gene and in the schroom family member 3 (<it>SCHROOM3</it>) gene were also replicated.</p> <p>Conclusions</p> <p>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 <it>SYT1 </it>and <it>GABRR2 </it>corroborate previous findings that highlighted a possible role of the neurotransmitters GABA_Areceptors in the regulation of the glomerular basement membrane and a possible interaction between GABA_Areceptors and synaptotagmin-I at the podocyte level.</p>