Stroke. 2005;36:731-736
Published online before print February 24, 2005,
doi: 10.1161/01.STR.0000157587.59821.87
(Stroke. 2005;36:731.)
© 2005 American Heart Association, Inc.
ALOX5AP Gene and the PDE4D Gene in a Central European Population of Stroke Patients
Elin Lõhmussaar, MSc;
Andreas Gschwendtner, MD;
Jakob C. Mueller, PhD;
Tõnis Org, MSc;
Erich Wichmann, PhD;
Gerhard Hamann, MD;
Thomas Meitinger, MD, PhD
Martin Dichgans, MD
From the Institutes of Human Genetics (E.L., J.C.M., T.O., T.M.) and Epidemiology (E.W.), GSF-National Research Institute for Environment and Health, Neuherberg, Germany; the Institute of Molecular and Cell Biology (E.L., T.O.), University of Tartu, Estonian Biocenter, Estonia; the Department of Neurology (A.G., G.H., M.D.), Klinikum of Großhadern, Munich, Germany; and the Institute of Human Genetics (T.M.), Technical University Munich, Germany.
Correspondence to Dr Martin Dichgans, Department of Neurology, Klinikum Großhadern Marchioninistr. 15 D-81377 München Germany. E-mail martin.dichgans{at}med.uni-muenchen.de
Background and Purpose— Recent evidence has implicated the genes for 5-lipoxygenase activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) as susceptibility genes for stroke in the Icelandic population. The aim of the present study was to explore the role of these genes in a central European population of stroke patients.
Methods— A total of 639 consecutive stroke patients and 736 unrelated population-based controls that had been matched for age and sex were examined using a case-control design. Twenty-two single-nucleotide polymorphisms (SNPs) covering ALOX5AP were genotyped. For PDE4D, microsatellite AC008818-1 and 12 SNPs, which tag all common haplotypes in previously identified linkage disequilibrium (LD) blocks, were analyzed.
Results— A nominally significant association with stroke was observed with several SNPs from ALOX5AP, including SNP SG13S114, which had been part of the Icelandic at-risk haplotype. Associations were stronger in males than in females, with SG13S114 (odds ratio, 1.24; 95% CI, 1.04 to 1.55; P=0.017) and SG13S100 (odds ratio, 1.26; 95% CI 1.03 to 1.54; P=0.024) showing the strongest associations. No significant associations were detected with single markers and haplotypes in PDE4D. The frequencies of single-marker alleles and haplotypes differed largely from those in the Icelandic population.
Conclusions— The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with stroke, particularly in males. Variants in the PDE4D gene are not a major risk factor for stroke in individuals from central Europe. Population differences in allele and haplotype frequencies as well as LD structure may contribute to the observed differences between populations.
Key Words: genetics • stroke
This article has been cited by other articles:
|
|
|
|
 
T. Matsushita, M. Kubo, K. Yonemoto, T. Ninomiya, K. Ashikawa, B. Liang, J. Hata, Y. Doi, T. Kitazono, S. Ibayashi, et al.
Lack of Association Between Variations of PDE4D and Ischemic Stroke in the Japanese Population
Stroke,
April 1, 2009;
40(4):
1245 - 1251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Zintzaras, P. Rodopoulou, and N. Sakellaridis
Variants of the Arachidonate 5-Lipoxygenase-Activating Protein (ALOX5AP) Gene and Risk of Stroke: A HuGE Gene-Disease Association Review and Meta-Analysis
Am. J. Epidemiol.,
March 1, 2009;
169(5):
523 - 532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Freilinger, S. Bevan, S. Ripke, A. Gschwendtner, P. Lichtner, B. Muller-Myhsok, H. -E. Wichmann, H. S. Markus, T. Meitinger, and M. Dichgans
Genetic Variation in the Lymphotoxin-Alpha Pathway and the Risk of Ischemic Stroke in European Populations
Stroke,
March 1, 2009;
40(3):
970 - 972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-S. Hsieh, S.-C. Yu, W.-T. Chung, Y.-M. Hsueh, F.-C. Chen, W.-T. Chiu, and H.-M. Lee
Phosphodiesterase 4D (PDE4D) Gene Variants and Risk of Ischemic Stroke in the Taiwanese Population
Lab Med,
February 1, 2009;
40(2):
87 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ye, Y. Lin, J. R. Perez-Polo, B. F. Uretsky, Z. Ye, B. C. Tieu, and Y. Birnbaum
Phosphorylation of 5-Lipoxygenase at Ser523 by Protein Kinase A Determines Whether Pioglitazone and Atorvastatin Induce Proinflammatory Leukotriene B4 or Anti-Inflammatory 15-Epi-Lipoxin A4 Production
J. Immunol.,
September 1, 2008;
181(5):
3515 - 3523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Gubitosi-Klug, R. Talahalli, Y. Du, J. L. Nadler, and T. S. Kern
5-Lipoxygenase, but Not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy
Diabetes,
May 1, 2008;
57(5):
1387 - 1393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Miller, P. M. Ridker, P. Libby, and D. J. Kwiatkowski
Atherosclerosis: The Path From Genomics to Therapeutics
J. Am. Coll. Cardiol.,
April 17, 2007;
49(15):
1589 - 1599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Lalouschek, G. Endler, M. Schillinger, K. Hsieh, W. Lang, S. Cheng, P. Bauer, O. Wagner, and C. Mannhalter
Candidate Genetic Risk Factors of Stroke: Results of a Multilocus Genotyping Assay
Clin. Chem.,
April 1, 2007;
53(4):
600 - 605.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K Luo, B. K Jefferson, M. J Garcia, G. S Ginsburg, and E. J Topol
Challenges in the phenotypic characterisation of patients in genetic studies of coronary artery disease
J. Med. Genet.,
March 1, 2007;
44(3):
161 - 165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dichgans and R. A. Hegele
Update on the Genetics of Stroke and Cerebrovascular Disease 2006
Stroke,
February 1, 2007;
38(2):
216 - 218.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. van Leyen, H. Y. Kim, S.-R. Lee, G. Jin, K. Arai, and E. H. Lo
Baicalein and 12/15-Lipoxygenase in the Ischemic Brain
Stroke,
December 1, 2006;
37(12):
3014 - 3018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Kamm, F. Asmus, J. Mueller, P. Mayer, M. Sharma, U. J. Muller, S. Beckert, R. Ehling, T. Illig, H. E. Wichmann, et al.
Strong genetic evidence for association of TOR1A/TOR1B with idiopathic dystonia
Neurology,
November 28, 2006;
67(10):
1857 - 1859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Topol, J. Smith, E. F. Plow, and Q. K. Wang
Genetic susceptibility to myocardial infarction and coronary artery disease
Hum. Mol. Genet.,
October 15, 2006;
15(suppl_2):
R117 - R123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J M Staton, M S Sayer, G J Hankey, J Attia, A Thakkinstian, Q Yi, V J Cole, R Baker, and J W Eikelboom
Association between phosphodiesterase 4D gene and ischaemic stroke.
J. Neurol. Neurosurg. Psychiatry,
September 1, 2006;
77(9):
1067 - 1069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Song, J. W. Cole, J. R. O'Connell, O. C. Stine, M. Gallagher, W. H. Giles, B. D. Mitchell, M. A. Wozniak, B. J. Stern, J. D. Sorkin, et al.
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study
Hum. Mol. Genet.,
August 15, 2006;
15(16):
2468 - 2478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Y.L. Zee, S. Cheng, H. H Hegener, H. A. Erlich, and P. M Ridker
Genetic Variants of Arachidonate 5-Lipoxygenase-Activating Protein, and Risk of Incident Myocardial Infarction and Ischemic Stroke: A Nested Case-Control Approach
Stroke,
August 1, 2006;
37(8):
2007 - 2011.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Y.L. Zee, V. H. Brophy, S. Cheng, H. H Hegener, H. A. Erlich, and P. M Ridker
Polymorphisms of the Phosphodiesterase 4D, cAMP-Specific (PDE4D) Gene and Risk of Ischemic Stroke: A Prospective, Nested Case-Control Evaluation
Stroke,
August 1, 2006;
37(8):
2012 - 2017.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Worrall and J. C. Mychaleckyj
PDE4D and Stroke: A Real Advance or a Case of the Emperor's New Clothes?
Stroke,
August 1, 2006;
37(8):
1955 - 1957.
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. H. Brophy, S. K. Ro, B. K. Rhees, L.-Y. Lui, J. M. Lee, N. Umblas, L. G. Bentley, J. Li, S. Cheng, W. S. Browner, et al.
Association of Phosphodiesterase 4D Polymorphisms With Ischemic Stroke in a US Population Stratified by Hypertension Status
Stroke,
June 1, 2006;
37(6):
1385 - 1390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Kuhlenbaumer, K Berger, A Huge, E Lange, C Kessler, U John, H Funke, D G Nabavi, F Stogbauer, E B Ringelstein, et al.
Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort
J. Neurol. Neurosurg. Psychiatry,
April 1, 2006;
77(4):
521 - 524.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Woo, R. Kaushal, B. Kissela, P. Sekar, M. Wolujewicz, P. Pal, K. Alwell, M. Haverbusch, I. Ewing, R. Miller, et al.
Association of Phosphodiesterase 4D With Ischemic Stroke: A Population-Based Case-Control Study
Stroke,
February 1, 2006;
37(2):
371 - 376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. S. Markus and M. J. Alberts
Update on Genetics of Stroke and Cerebrovascular Disease 2005
Stroke,
February 1, 2006;
37(2):
288 - 290.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nakayama, S. Asai, N. Sato, and M. Soma
Genotype and Haplotype Association Study of the STRK1 Region on 5q12 Among Japanese: A Case-Control Study
Stroke,
January 1, 2006;
37(1):
69 - 76.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Saleheen, S. Bukhari, S. R. Haider, A. Nazir, S. Khanum, S. Shafqat, M. K. Anis, and P. Frossard
Association of Phosphodiesterase 4D Gene With Ischemic Stroke in a Pakistani Population
Stroke,
October 1, 2005;
36(10):
2275 - 2277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Houslay
The Long and Short of Vascular Smooth Muscle Phosphodiesterase-4 As a Putative Therapeutic Target
Mol. Pharmacol.,
September 1, 2005;
68(3):
563 - 567.
[Abstract]
[Full Text]
[PDF]
|
|
|
