Abstract
The transcription factor GATA2 was reported to associate with coronary artery disease (CAD) in the family-based Genecard sample (Connelly et al. in PLoS Genet 2:e139, 2006). We asked whether GATA2 associates with sporadic cases of CAD in the Ottawa Heart Genomics Study (OHGS) and Cleveland Clinic (CC) populations. We genotyped the lead single nucleotide polymorphism (SNP) from Genecard, rs2713604 which is located in intron 5–6 of GATA2 in 600 CAD cases and 625 controls, as well as a tag SNP rs1573949 (r 2 = 0.87 in Caucasians of European ancestry in Utah from HapMap) in 1,136 cases and 1,162 controls in the OHGS1 population. A further 1,838 CAD cases and 913 controls derived from an independent sample combining genotypes from CC and OHGS2 populations were genotyped for rs1573949. Neither of the genotyped SNPs associates with CAD in the OHGS1 or CC/OHGS2 populations. Our data suggest that GATA2 does not contribute to the development of angiographic CAD among sporadic cases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Clarke R, Xu P, Bennett D, Lewington S, Zondervan K, Parish S, Palmer A, Clark S, Cardon L, Peto R, Lathrop M, Collins R (2006) Lymphotoxin-alpha gene and risk of myocardial infarction in 6, 928 cases and 2, 712 controls in the ISIS case-control study. PLoS Genet 2:e107
Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354:1264–1272
Connelly JJ, Wang T, Cox JE, Haynes C, Wang L, Shah SH, Crosslin DR, Hale AB, Nelson S, Crossman DC, Granger CB, Haines JL, Jones CJ, Vance JM, Goldschmidt-Clermont PJ, Kraus WE, Hauser ER, Gregory SG (2006) GATA2 is associated with familial early-onset coronary artery disease. PLoS Genet 2:e139
Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316:1491–1493
Horne BD, Hauser ER, Wang L, Muhlestein JB, Anderson JL, Carlquist JF, Shah SH, Kraus WE (2009) Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking. Ann Hum Genet 73(Pt 6):551–558
Kathiresan S (2008) A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction. N Engl J Med 358:2299–2300
Koch W, Hoppmann P, Mueller JC, Schomig A, Kastrati A (2008) Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population. Nat Genet 40:1386–1387 author reply 1387–1388
Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott M, Meigs J, Mozaffarian D, Nichol G, O’Donnell C, Roger V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T, Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y (2009) Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119:480–486
McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488–1491
Murabito JM, Pencina MJ, Nam BH, D’Agostino RB Sr, Wang TJ, Lloyd-Jones D, Wilson PW, O’Donnell CJ (2005) Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA 294:3117–3123
Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 349:1498–1504
Ozaki K, Ohnishi Y, Iida A, Sekine A, Yamada R, Tsunoda T, Sato H, Hori M, Nakamura Y, Tanaka T (2002) Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction. Nat Genet 32:650–654
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genomewide association studies. Nat Genet 38:904–909
Rissanen AM (1979) Familial occurrence of coronary heart disease: effect of age at diagnosis. Am J Cardiol 44:60–66
Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453
Shea S, Ottman R, Gabrieli C, Stein Z, Nichols A (1984) Family history as an independent risk factor for coronary artery disease. J Am Coll Cardiol 4:793–801
ten Kate LP, Boman H, Daiger SP, Motulsky AG (1982) Familial aggregation of coronary heart disease and its relation to known genetic risk factors. Am J Cardiol 50:945–953
Thomas CB, Cohen BH (1955) The familial occurrence of hypertension and coronary artery disease, with observations concerning obesity and diabetes. Ann Intern Med 42:90–127
Wang X, Ria M, Kelmenson PM, Eriksson P, Higgins DC, Samnegard A, Petros C, Rollins J, Bennet AM, Wiman B, de Faire U, Wennberg C, Olsson PG, Ishii N, Sugamura K, Hamsten A, Forsman-Semb K, Lagercrantz J, Paigen B (2005) Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet 37:365–372
Acknowledgments
This research was supported by grants from the Canadian Institutes of Health Research #MOP82810, #NA6650, #MOP77682, the Canada Foundation for Innovation CFI #11966, the Heart and Stroke Foundation of Ontario #NA6001, the National Institutes of Health grants P01HL087018, P01 HL076491 and P01 HL077107 (S.L.H.) and the Cleveland Clinic Clinical Research Unit of the Cleveland Clinic/Case Western Reserve University CTSA (1UL1RR024989).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dandona, S., Chen, L., Fan, M. et al. The transcription factor GATA-2 does not associate with angiographic coronary artery disease in the Ottawa Heart Genomics and Cleveland Clinic GeneBank Studies. Hum Genet 127, 101–105 (2010). https://doi.org/10.1007/s00439-009-0761-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-009-0761-3