title: Epistatic interaction between common AGT G(-6)A (rs5051) and AGTR1 A1166C (rs5186) variants contributes to variation in kidney size at birth.
abstract: Low nephron number has been recognised as an important cardiovascular risk factor and recently a strong correlation between renal mass and nephron number has been demonstrated in newborns. The aim of this study was to investigate individual, as well as combined, effects of common variants of genes which encode for major components of the renin-angiotensin system (REN G10601A, AGT G(-6)A, ACE I/D, AGTR1 A1166C) on kidney size in healthy, full-term newborns. A significant additive main effect of the ACE I/D polymorphism, as well as an additive-by-additive interaction between AGT G(-6)A and AGTR1 A1166C variants, were found. The variance attributed to the epistatic effect was 27.9 ml(2)/m(4), which accounted for 73.8% of the interaction variance (37.8 ml(2)/m(4)), 66.4% of the genetic variance (42.0 ml(2)/m(4)) and 4.4% to the total phenotypic variance (628 ml(2)/m(4)). No other statistically significant main or epistatic effects were detected. Our results highlight the importance of considering gene-gene interactions as part of the genetic architecture of congenital nephron number, even when the loci do not show significant single locus effects. Unravelling the genetic determinants of low nephron number, along with early molecular screening, may well help to identify children at risk for cardiovascular disease.
authors.affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland. Electronic address: mariush@pum.edu.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kaczmarczyk
authors.affiliation: Department of Radiology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuprjanowicz
authors.affiliation: Department of Neonatal Diseases, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Łoniewska
authors.affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Gorący
authors.affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Taryma-Leśniak
authors.affiliation: Department of Gerontobiology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Skonieczna-Żydecka
authors.affiliation: Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ciechanowicz
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities / Q000033:anatomy & histology*; D008297:Male; D008957:Models, Genetic; D009399:Nephrons / Q000002:abnormalities / Q000033:anatomy & histology; D009929:Organ Size / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C534931:AGT protein, human; C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen
keywords: Epistasis; Genetic architecture of traits; Gene–gene interactions; Kidney size; Number of nephrons