BMC Medical Genetics (Mar 2010)

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

  • 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

DOI
https://doi.org/10.1186/1471-2350-11-41
Journal volume & issue
Vol. 11, no. 1
p. 41

Abstract

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Abstract Background Serum creatinine (SCR) 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 SCR level is explicable by genetic factors. Methods We performed a meta-analysis of genome-wide association studies of SCR 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 × 10-6 and 1.7 × 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 × 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 GABAAreceptors and synaptotagmin-I at the podocyte level.