Genome-wide association study identifies 3 genomic loci significantly associated with serum levels of homoarginine: The atheroremo consortium

Circulation: Cardiovascular Genetics

Volumn 6, Issue 5, 2013, Pages 505-513

  Kleber, Marcus E ^a,b   Seppälä, Ilkka ^c   Pilz, Stefan ^d,e   Hoffmann, Michael M ^e   Tomaschitz, Andreas ^e   Oksala, Niku ^c,f   Raitoharju, Emma ^c   Lyytikäinen, Leo Pekka ^c   Mäkelä, Kari Matti ^c   Laaksonen, Reijo ^c   Kähönen, Mika ^g   Raitakari, Olli T ^c   Huang, Jie ^h   Kienreich, Katharina ^e   Fahrleitner Pammer, Astrid ^a   Drechsler, Christiane ⁱ   Krane, Vera ⁱ   Boehm, Bernhard O ^j,k,m   Koenig, Wolfgang ^a   Wanner, Christoph ⁱ   Lehtimäki, Terho ^c   März, Winfried ^b,l,n   Meinitzer, Andreas ^e   more..

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^e MEDICAL UNIVERSITY OF GRAZ   (Austria)

^f UNIVERSITY OF FREIBURG   (Germany)

^g TAMPERE UNIVERSITY HOSPITAL   (Finland)

^h UNIVERSITY OF TURKU   (Finland)

ⁱ TURKU UNIVERSITY HOSPITAL   (Finland)

^j WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^k UNIVERSITY OF WÜRZBURG   (Germany)

^l UNIVERSITY OF ULM   (Germany)

^m IMPERIAL COLLEGE LONDON   (United Kingdom)

ⁿ SYNLAB ACADEMY   (Germany)

more..

Author keywords

Amino acids; Arteriosclerosis; Cardiovascular diseases; Genome wide association study

Indexed keywords

ARGININE; HOMOARGININE;

ADULT; ALANINE GLYOXYLATE AMINOTRANSFERASE GENE; AMINO ACID BLOOD LEVEL; ANGIOCARDIOGRAPHY; ARTICLE; CARBAMOYL PHOSPHATE SYNTHASE GENE; CHROMOSOME 2; CHROMOSOME 5; FEMALE; GENE; GENE EXPRESSION; GENE LOCUS; GENETIC ASSOCIATION; GLYCINE AMIDINOTRANSFERASE GENE; HUMAN; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MITOCHONDRION; MORTALITY; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

AMINO ACIDS; ARTERIOSCLEROSIS; CARDIOVASCULAR DISEASES; GENOME-WIDE ASSOCIATION STUDY;

ADULT; AGED; ARGININE; CARDIOVASCULAR DISEASES; CHROMOSOMES, HUMAN; ENZYMES; FEMALE; GENETIC LOCI; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HOMOARGININE; HUMANS; MALE; MIDDLE AGED; MITOCHONDRIA; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84892392892     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.113.000108     Document Type: Article

References (45)

1. Hrabák A, Bajor T, Temesi A. Comparison of substrate and inhibitor specificity of arginase and nitric oxide (NO) synthase for arginine analogues and related compounds in murine and rat macrophages. Biochem Biophys Res Commun. 1994;198:206-212.
2. Valtonen P, Laitinen T, Lyyra-Laitinen T, Raitakari OT, Juonala M, Viikari JS, et al. Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circ J. 2008;72:1879-1884.
3. März W, Meinitzer A, Drechsler C, Pilz S, Krane V, Kleber ME, et al. Homoarginine, cardiovascular risk, and mortality. Circulation. 2010;122:967-975.
4. Pilz S, Tomaschitz A, Meinitzer A, Drechsler C, Ritz E, Krane V, et al. Low serum homoarginine is a novel risk factor for fatal strokes in patients undergoing coronary angiography. Stroke. 2011;42:1132-1134.
5. Drechsler C, Meinitzer A, Pilz S, Krane V, Tomaschitz A, Ritz E, et al. Homoarginine, heart failure, and sudden cardiac death in haemodialysis patients. Eur J Heart Fail. 2011;13:852-859.
6. Pilz S, Meinitzer A, Tomaschitz A, Drechsler C, Ritz E, Krane V, et al. Low homoarginine concentration is a novel risk factor for heart disease. Heart. 2011;97:1222-1227.
7. Ryan WL, Johnson RJ, Dimari S. Homoarginine synthesis by rat kidney. Arch Biochem Biophys. 1969;131:521-526.
8. Ryan WL, Wells IC. Homocitrulline and homoarginine synthesis from lysine. Science. 1964;144:1122-1127.
9. Pilz S, Meinitzer A, Tomaschitz A, Kienreich K, Dobnig H, Schwarz M, et al. Associations of homoarginine with bone metabolism and density, muscle strength and mortality: cross-sectional and prospective data from 506 female nursing home patients. Osteoporos Int. 2013;24:377-381.
10. Pilz S, Meinitzer A, Tomaschitz A, Kienreich K, Fahrleitner-Pammer A, Drechsler C, et al. Homoarginine deficiency is associated with increased bone turnover. Osteoporos Int. 2012;23:2731-2732.
11. Davids M, Ndika JD, Salomons GS, Blom HJ, Teerlink T. Promiscuous activity of arginine:glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine. FEBS Lett. 2012;586:3653-3657.
12. Wanner C, Krane V, März W, Olschewski M, Asmus HG, Krämer W, et al Deutsche Diabetes-Dialyse-Studie (4D) Study Group. Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. Kidney Blood Press Res. 2004;27:259-266.
13. Pilz S, Tomaschitz A, Stepan V, Obermayer-Pietsch B, Fahrleitner-Pammer A, Schweighofer N, et al. Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism. BMC Endocr Disord. 2009;9:11.
14. Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, et al LURIC Study Group (Ludwigshafen Risk and Cardiovascular Health). Rationale and design of the LURIC study-A resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics. 2001;2(1 Suppl 1):S1-S73.
15. Raitakari OT, Juonala M, Rönnemaa T, Keltikangas-Järvinen L, Räsänen L, Pietikäinen M, et al. Cohort profile: the cardiovascular risk in Young Finns Study. Int J Epidemiol. 2008;37:1220-1226.
16. Nieminen T, Lehtinen R, Viik J, Lehtimäki T, Niemelä K, Nikus K, et al. The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality. BMC Cardiovasc Disord. 2006;6:9.
17. Moore S, Spackman DH, Stein WH. Automatic recording apparatus for use in the chromatography of amino acids. Fed Proc. 1958;17:1107-1115.
18. Carling RS, Hogg SL, Wood TC, Calvin J. Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by underivatized liquid chromatography-tandem mass spectrometry. Ann Clin Biochem. 2008;45(Pt 6):575-584.
19. Meinitzer A, Puchinger M, Winklhofer-Roob BM, Rock E, Ribalta J, Roob JM, et al. Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method. Clin Chim Acta. 2007;384:141-148.
20. Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA. Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem. 2002;303:131-137.
21. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010;34:816-834.
22. Li Y, Willer C, Sanna S, Abecasis G. Genotype imputation. Annu Rev Genomics Hum Genet. 2009;10:387-406.
23. Aulchenko YS, Struchalin MV, van Duijn CM. ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics. 2010;11:134.
24. Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics. 2010;26:2336-2337.
25. Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190-2191.
26. Yang TP, Beazley C, Montgomery SB, Dimas AS, Gutierrez-Arcelus M, Stranger BE, et al. Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics. 2010;26:2474-2476.
27. da Silva RP, Nissim I, Brosnan ME, Brosnan JT. Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. Am J Physiol Endocrinol Metab. 2009;296:E256-E261.
28. Item CB, Stöckler-Ipsiroglu S, Stromberger C, Mühl A, Alessandrì MG, Bianchi MC, et al. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001;69:1127-1133.
29. Choe CU, Nabuurs C, Stockebrand MC, Neu A, Nunes P, Morellini F, et al. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome. Hum Mol Genet. 2013;22:110-123.
30. Schulze A. Creatine deficiency syndromes. Mol Cell Biochem. 2003;244:143-150.
31. Cullen ME, Yuen AH, Felkin LE, Smolenski RT, Hall JL, Grindle S, et al. Myocardial expression of the arginine:glycine amidinotransferase gene is elevated in heart failure and normalized after recovery: potential implications for local creatine synthesis. Circulation. 2006;114(1 Suppl):I16-I20.
32. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248-249.
33. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073-1081.
34. Ward LD, Kellis M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 2012;40(Database issue):D930-D934.
35. Häberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, et al Urea Cycle Disorders Consortium. Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Hum Mutat. 2011;32:579-589.
36. Summar ML, Hall L, Christman B, Barr F, Smith H, Kallianpur A, et al. Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I. Mol Genet Metab. 2004;81(Suppl 1):S12-S19.
37. Summar ML, Gainer JV, Pretorius M, Malave H, Harris S, Hall LD, et al. Relationship between carbamoyl-phosphate synthetase genotype and systemic vascular function. Hypertension. 2004;43:186-191.
38. Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Glazer NL, et al. New loci associated with kidney function and chronic kidney disease. Nat Genet. 2010;42:376-384.
39. Paré G, Chasman DI, Parker AN, Zee RR, Mälarstig A, Seedorf U, et al. Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study. Circ Cardiovasc Genet. 2009;2:142-150.
40. Pearson DL, Dawling S, Walsh WF, Haines JL, Christman BW, Bazyk A, et al. Neonatal pulmonary hypertension-urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med. 2001;344:1832-1838.
41. Lee IS, Muragaki Y, Ideguchi T, Hase T, Tsuji M, Ooshima A, et al. Molecular cloning and sequencing of a cDNA encoding alanine-glyoxylate aminotransferase 2 from rat kidney. J Biochem. 1995;117:856-862.
42. Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem. 1989;264:10205-10209.
43. Rodionov RN, Murry DJ, Vaulman SF, Stevens JW, Lentz SR. Human alanine-glyoxylate aminotransferase 2 lowers asymmetric dimethylarginine and protects from inhibition of nitric oxide production. J Biol Chem. 2010;285:5385-5391.
44. Suhre K, Wallaschofski H, Raffler J, Friedrich N, Haring R, Michael K, et al. A genome-wide association study of metabolic traits in human urine. Nat Genet. 2011;43:565-569.
45. Caplin B, Wang Z, Slaviero A, Tomlinson J, Dowsett L, Delahaye M, et al International Consortium for Blood Pressure Genome-Wide Association Studies. Alanine-glyoxylate aminotransferase-2 metabolizes endogenous methylarginines, regulates NO, and controls blood pressure. Arterioscler Thromb Vasc Biol. 2012;32:2892-2900.