Published Online
on May 4, 2006

A more recent version of this article appeared on June 1, 2006

This Article Full Text (PDF) All Versions of this Article: 37/6/1385    most recent 01.STR.0000221788.10723.66v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brophy, V. H. Articles by Erlich, H. A. Search for Related Content PubMed PubMed Citation Articles by Brophy, V. H. Articles by Erlich, H. A. Related Collections Cerebrovascular disease/stroke Genetics of Stroke

Submitted on February 2, 2006
Revised on March 9, 2006
Accepted on March 29, 2006

Association of Phosphodiesterase 4D Polymorphisms With Ischemic Stroke in a US Population Stratified by Hypertension Status

Victoria H. Brophy PhD^*; Sunhee K. Ro PhD; Brian K. Rhees PhD; Li-Yung Lui MA, MS; Jocelyn M. Lee BS; Nanette Umblas BS; L. Gordon Bentley MSc; Jia Li PhD; Suzanne Cheng PhD; Warren S. Browner MD; and Henry A. Erlich PhD

From Roche Molecular Systems (V.H.B., S.K.R., B.K.R., J.M.L., N.U., L.G.B., J.L., S.C., H.A.E.), Alameda, Calif; and California Pacific Medical Center Research Institute (L.-Y.L., W.S.B.), San Francisco, Calif.

^* To whom correspondence should be addressed. E-mail: victoria_h.brophy{at}roche.com.

Background and Purpose--Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States.

Methods--The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.4 years of follow-up were compared with 560 controls.

Results--Marginal associations with stroke (P<0.10) were found for 3 polymorphisms. Stratification of the population by hypertension markedly strengthened the association. SNPs 9 (hazard ratio [HR], 0.48; 95% CI, 0.26 to 0.91), 42 (HR, 1.73; 95% CI, 1.10 to 2.70), 219 (HR, 1.73; 95% CI, 1.13 to 2.64), and 220 (HR, 1.56; 95% CI, 1.05 to 2.32) showed significant association with stroke (P<0.05) under a dominant model in subjects without hypertension at baseline, and SNP 175 was significantly associated with stroke under an additive model (HR, 0.76; 95% CI, 0.59 to 0.98) in subjects with hypertension. Furthermore, the microsatellite AC008818-1 showed association with stroke only in the nonhypertensive subjects. Based on results in Iceland, specific haplotypes were tested in SOF, and stratification by hypertension also affected these association results.

Conclusion--These data are consistent with an association of the PDE4D gene with stroke in a non-Icelandic sample and suggest an effect of hypertension status.

Key words: genetics • hypertension • polymorphism • stroke

This article has been cited by other articles:

				S. Bevan, M. Dichgans, A. Gschwendtner, G. Kuhlenbaumer, E.B. Ringelstein, and H. S. Markus Variation in the PDE4D Gene and Ischemic Stroke Risk: A Systematic Review and Meta-analysis on 5200 Cases and 6600 Controls Stroke, July 1, 2008; 39(7): 1966 - 1971. [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]

				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]