Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic stroke

Xue, Hao; Hu, Wang; Song, Xiaodong; Li, Weiju; Sun, Kai; Zhang, Weili; Wang, Xiaojian; Wang, Yibo; Hui, Rutai

doi:10.1042/cs20080162

Cited by 33 publications

(25 citation statements)

References 20 publications

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“…Subsequently, Bevan et al [83] performed a study in a non-Icelandic European population and found a possible association with CE stroke, but the lack of an association found with carotid IMT and plaque would suggest a mechanism other than accelerated atherosclerosis. However, the role of PDE4D is inconclusive, with some investigators [84,85] replicating the association and some not [86] . Despite extensive genotyping of the PDE4D locus, the disease-causing genetic variant has not been identified thus far.…”

Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

Genetics of stroke

Guo

Liu

2010

Acta Pharmacol Sin

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Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multifactorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Studies of stroke as a monogenic disease have made huge progress, and animal models serve as an indispensable tool to dissect the complex genetics of stroke. In the present review, we provide insight into the role of in vivo stroke models for the study of stroke genetics.

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Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

Genetics of stroke

Guo

Liu

2010

Acta Pharmacol Sin

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“…Also, it seems possible that the effect of PDE4D on stroke varies between populations depending on different genetic backgrounds and environmental influences [34]. The study by Xue et al demonstrated that allele C of rs966221 in PDE4D gene conferred a 1.5-fold risk for atherothrombotic strokes in a Chinese population [35], supporting that PDE4D acts through atherosclerosis. 4.7 ALOX5AP and the leukotriene pathway ALOX5AP is another gene that has been discovered through genome-wide linkage analysis.…”

Section: Phosphodiesterase 4dmentioning

confidence: 97%

Genetics of ischemic and hemorrhagic stroke in Chinese population

Zhang¹,

Hui

2010

Front. Med. China

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Stroke is a major cause of adult death and disability worldwide. Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors, but the identification of individual causative variants remains little known. Genetic influences are likely to be polygenic with small effect sizes, and stroke itself consists of a number of different subtypes which may each have different genetic profiles. In addition, various ethnic populations may have different stroke risk, such as Asian race. The reasons for high risk of stroke among the Chinese, especially hemorrhagic stroke, remain unknown. Most human studies have taken a candidate gene approach using case-control methodology. To be reliably detected, small relative risks require large sample sizes, probably 1000 patients or more. Genome-wide association (GWA) study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases. Recently, a multistage GWA study has identified three loci on chromosomes 2q, 8q and 9p to be associated with intracranial aneurysm in European and Japanese populations. Another GWA finding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations. In this review, we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population. The combined effects of multiple susceptibility genes for stroke risk are also summarized.

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“…In this meta-analysis, we included 7 more studies (i.e. Lövkvist et al [16] , Matsushita et al [29] , Lin et al [31] , Banerjee et al [32] , Munshi et al [33] , Xue et al [34] , and Sun et al [35] ) published after the study by Bevan et al [17] . Among the 6 SNPs analyzed, our metaanalysis of 7 homogenous studies showed a significant association between SNP56 and ischemic stroke (p = 0.022).…”

Section: Discussionmentioning

confidence: 99%

“…We performed a meta-analysis in Asian groups (i.e. Matsushita et al [29] , Saleheen et al [30] , Lin et al [31] , Xue et al [34] , and Sun et al [35] ) and found no evidence of a genetic association of SNP87 with ischemic stroke. After removing Staton et al [13] from the initial analysis, the heterogeneity of SNP89 significantly decreased.…”

Section: Studymentioning

confidence: 99%

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Meta-Analysis of Homogeneous Subgroups Reveals Association between <i>PDE4D</i> Gene Variants and Ischemic Stroke

Yoon¹,

Park²,

Kang³

et al. 2011

Neuroepidemiology

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Background: An Icelandic study showed a significant positive association between phosphodiesterase 4D (PDE4D) gene variants and stroke. However, subsequent studies reported conflicting results, possibly due to small sample sizes and the heterogeneity of the studies. Method: We performed a meta-analysis on 6 SNPs of the PDE4D gene to investigate the association between this gene and ischemic stroke by integrating the results of previous studies, comprising 11,834 cases and 15,233 controls. A pooled genotypic odds ratio (OR) for each SNP was determined under 3 genetic models (i.e. dominant, recessive, and codominant) using both fixed- and random-effects models with consideration for heterogeneity and publication bias across studies. Results: Among the SNPs included in this study, SNP56 (rs702553) showed the most significant association with ischemic stroke in a meta-analysis comprised of 7 homogenous studies. The overall OR of the TT genotype compared to the AA genotype was 1.29 (95% CI 1.03–1.61; p = 0.022). For SNP83 (rs966221), a protective effect of the ancestral allele T was observed only in Asian populations (ORTT 0.79, 95% CI 0.69–0.90; p = 0.0005). This meta-analysis revealed a significant association of PDE4D gene variants with the risk of ischemic stroke, and further investigations are warranted to evaluate possible ethnic-specific effects.

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Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic stroke

Cited by 33 publications

References 20 publications

Genetics of stroke

Genetics of stroke

Genetics of ischemic and hemorrhagic stroke in Chinese population

Meta-Analysis of Homogeneous Subgroups Reveals Association between <i>PDE4D</i> Gene Variants and Ischemic Stroke

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