title: Genome-wide association study identifies 3 genomic loci significantly associated with serum levels of homoarginine: the AtheroRemo Consortium.
abstract: BACKGROUND
  Low serum levels of the amino acid derivative, homoarginine, have been associated with increased risk of total and cardiovascular mortality. Homoarginine deficiency may be related to renal and heart diseases, but the pathophysiologic role of homoarginine and the genetic regulation of its serum levels are largely unknown.
  
  
  RESULTS
  In 3041 patients of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study referred for coronary angiography and 2102 participants of the Young Finns Study (YFS), we performed a genome-wide association study to identify genomic loci associated with homoarginine serum levels and tested for associations of identified single-nucleotide polymorphisms with mortality in LURIC. We found genome-wide significant associations with homoarginine serum levels on chromosome 2 at the carbamoyl phosphate synthetase I locus, on chromosome 5 at the alanine-glyoxylate aminotransferase 2 locus, and on chromosome 15 at the glycine amidinotransferase locus, as well as a suggestive association on chromosome 6 at the Homo sapiens mediator complex subunit 23 gene/arginase I locus. All loci harbor enzymes located in the mitochondrium are involved in arginine metabolism. The strongest association was observed for rs1153858 at the glycine amidinotransferase locus with a P value of 1.25E-45 in the combined analysis and has been replicated in both the Die Deutsche Diabetes Dialyse Studie (4D study) and the Graz Endocrine Causes of Hypertension (GECOH) study.
  
  
  CONCLUSIONS
  In our genome-wide association study, we identified 3 chromosomal regions significantly associated with serum homoarginine and another region with suggestive association, providing novel insights into the genetic regulation of homoarginine.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.forename: Leo-Pekka
authors.initials: LP
authors.lastname: Lyytikäinen
authors.forename: Kari-Matti
authors.initials: KM
authors.lastname: Mäkelä
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Katharina
authors.initials: K
authors.lastname: Kienreich
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D002877:Chromosomes, Human / Q000235:genetics; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D004798:Enzymes; D006709:Homoarginine; D001120:Arginine
keywords: amino acids; arteriosclerosis; cardiovascular diseases; genome-wide association study