Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study
An association between polymorphisms within the phosphodiesterase 4D gene ( PDE4D ) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations. In the present study, we examined the association between PDE4...
Published in: | Human Molecular Genetics |
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fthighwire:oai:open-archive.highwire.org:hmg:ddl169v1 2023-05-15T16:51:56+02:00 Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study Song, Qing Cole, John W. O'Connell, Jeffrey R. Stine, Oscar C. Gallagher, Margaret Giles, Wayne H. Mitchell, Braxton D. Wozniak, Marcella A. Stern, Barney J. Sorkin, John D. McArdle, Patrick F. Naj, Adam C. Xu, Qin Gibbons, Gary H. Kittner, Steven J. 2006-07-11 04:13:29.0 text/html http://hmg.oxfordjournals.org/cgi/content/short/ddl169v1 https://doi.org/10.1093/hmg/ddl169 en eng Oxford University Press http://hmg.oxfordjournals.org/cgi/content/short/ddl169v1 http://dx.doi.org/10.1093/hmg/ddl169 Copyright (C) 2006, Oxford University Press Article TEXT 2006 fthighwire https://doi.org/10.1093/hmg/ddl169 2013-05-27T20:53:54Z An association between polymorphisms within the phosphodiesterase 4D gene ( PDE4D ) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations. In the present study, we examined the association between PDE4D polymorphisms and early-onset ischemic stroke in a biracial female population. A systematic search for polymorphisms in the highly evolutionary conserved regions of PDE4D was performed on 48 African-American and 48 Caucasian participants. Novel and known polymorphisms were then prioritized and genotyped in the entire study population of 224 cases of first ischemic stroke among women aged 15-49 and 211 age- and ethnicity-balanced control subjects. Forty novel and previously reported polymorphisms with a minor allele frequency greater than 0.05 were determined, with twenty-three polymorphisms selected for analysis in the full case-control sample. SNP, linkage disequilibrium, and haplotype analyses were performed. SNP rs918592, found in an intron near the 5' end of the gene, was significantly associated with stroke (age- and race-adjusted odds ratio (OR = 1.5, p = 0.007), with 4 other SNPs showing significant, albeit less strong, associations. The magnitude of association was similar across African-Americans and Caucasians, and across multiple stroke subtypes (e.g., atherosclerotic, lacunar, and non-lacunar of undetermined etiology). The association of rs918592 with stroke was confined exclusively to current smokers (OR = 3.2, p = 0.00014), with no association observed among never-smokers (OR = 0.9, p = 0.75) or former smokers (OR = 1.2, p = 0.66), demonstrating a gene-environment interaction (p = 0.03). A strong dose-response relationship was also seen among current smokers. No specific risk haplotypes were identified. Text Iceland HighWire Press (Stanford University) Human Molecular Genetics 15 16 2468 2478 |
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HighWire Press (Stanford University) |
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Article Song, Qing Cole, John W. O'Connell, Jeffrey R. Stine, Oscar C. Gallagher, Margaret Giles, Wayne H. Mitchell, Braxton D. Wozniak, Marcella A. Stern, Barney J. Sorkin, John D. McArdle, Patrick F. Naj, Adam C. Xu, Qin Gibbons, Gary H. Kittner, Steven J. Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
topic_facet |
Article |
description |
An association between polymorphisms within the phosphodiesterase 4D gene ( PDE4D ) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations. In the present study, we examined the association between PDE4D polymorphisms and early-onset ischemic stroke in a biracial female population. A systematic search for polymorphisms in the highly evolutionary conserved regions of PDE4D was performed on 48 African-American and 48 Caucasian participants. Novel and known polymorphisms were then prioritized and genotyped in the entire study population of 224 cases of first ischemic stroke among women aged 15-49 and 211 age- and ethnicity-balanced control subjects. Forty novel and previously reported polymorphisms with a minor allele frequency greater than 0.05 were determined, with twenty-three polymorphisms selected for analysis in the full case-control sample. SNP, linkage disequilibrium, and haplotype analyses were performed. SNP rs918592, found in an intron near the 5' end of the gene, was significantly associated with stroke (age- and race-adjusted odds ratio (OR = 1.5, p = 0.007), with 4 other SNPs showing significant, albeit less strong, associations. The magnitude of association was similar across African-Americans and Caucasians, and across multiple stroke subtypes (e.g., atherosclerotic, lacunar, and non-lacunar of undetermined etiology). The association of rs918592 with stroke was confined exclusively to current smokers (OR = 3.2, p = 0.00014), with no association observed among never-smokers (OR = 0.9, p = 0.75) or former smokers (OR = 1.2, p = 0.66), demonstrating a gene-environment interaction (p = 0.03). A strong dose-response relationship was also seen among current smokers. No specific risk haplotypes were identified. |
format |
Text |
author |
Song, Qing Cole, John W. O'Connell, Jeffrey R. Stine, Oscar C. Gallagher, Margaret Giles, Wayne H. Mitchell, Braxton D. Wozniak, Marcella A. Stern, Barney J. Sorkin, John D. McArdle, Patrick F. Naj, Adam C. Xu, Qin Gibbons, Gary H. Kittner, Steven J. |
author_facet |
Song, Qing Cole, John W. O'Connell, Jeffrey R. Stine, Oscar C. Gallagher, Margaret Giles, Wayne H. Mitchell, Braxton D. Wozniak, Marcella A. Stern, Barney J. Sorkin, John D. McArdle, Patrick F. Naj, Adam C. Xu, Qin Gibbons, Gary H. Kittner, Steven J. |
author_sort |
Song, Qing |
title |
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
title_short |
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
title_full |
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
title_fullStr |
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
title_full_unstemmed |
Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
title_sort |
phosphodiesterase 4d polymorphisms and the risk of cerebral infarction in a biracial population: the stroke prevention in young women study |
publisher |
Oxford University Press |
publishDate |
2006 |
url |
http://hmg.oxfordjournals.org/cgi/content/short/ddl169v1 https://doi.org/10.1093/hmg/ddl169 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://hmg.oxfordjournals.org/cgi/content/short/ddl169v1 http://dx.doi.org/10.1093/hmg/ddl169 |
op_rights |
Copyright (C) 2006, Oxford University Press |
op_doi |
https://doi.org/10.1093/hmg/ddl169 |
container_title |
Human Molecular Genetics |
container_volume |
15 |
container_issue |
16 |
container_start_page |
2468 |
op_container_end_page |
2478 |
_version_ |
1766042064483516416 |