Dataset Information

No Association Between Single-Nucleotide Polymorphism 56 (SNP56) in Phosphodiesterase 4D (PDE4D) Gene and Susceptibility to Ischemic Stroke: A Meta-Analysis of 15 Studies.

ABSTRACT: BACKGROUND Recent studies demonstrated that polymorphisms in the PDE4D gene were associated with several processes involved in the occurrence of ischemic stroke (IS). The association between specific PDE4D single-nucleotide polymorphism 56 (SNP56) and IS risk was initially identified via genome-wide association studies (GWAS), although the GWAS in different populations produced inconclusive results. Thus, we performed a meta-analysis to better explain the association between PDE4D SNP56 and IS risk. MATERIAL AND METHODS A literature search was conducted using PubMed, Embase, and Web of Science up to June 1, 2015. A fixed-effects or random-effects model was used to calculate the pooled odds ratios (ORs) based on the results from the heterogeneity tests. RESULTS Finally, we performed a meta-analysis of 15 studies, involving 8731 IS patients and 10,756 controls. The results showed nonsignificant association between PDE4D SNP56 and IS risk (T vs. A: OR=1.01, 95%CI=0.88-1.15, P=0.90). Similarly, in the subgroup analysis by ethnicity, no significant association was observed in Asian (T vs. A: OR=1.08, 95%CI=0.80-1.44, P=0.62) or European (T vs. A: OR=0.96, 95%CI=0.86-1.08, P=0.54) population. Moreover, funnel plots and Egger regression testing showed no evidence of publication bias. CONCLUSIONS In summary, current evidence suggested that PDE4D SNP56 might not be associated with an increased susceptibility to IS. However, this conclusion needs further validation by well-designed studies with large sample sizes.

SUBMITTER: Zhang XY

PROVIDER: S-EPMC5083063 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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No Association Between Single-Nucleotide Polymorphism 56 (SNP56) in Phosphodiesterase 4D (PDE4D) Gene and Susceptibility to Ischemic Stroke: A Meta-Analysis of 15 Studies.

Zhang Xin-Yong XY Wan Qi Q Zhu Dong-Ya DY

Medical science monitor : international medical journal of experimental and clinical research 20161019

BACKGROUND Recent studies demonstrated that polymorphisms in the PDE4D gene were associated with several processes involved in the occurrence of ischemic stroke (IS). The association between specific PDE4D single-nucleotide polymorphism 56 (SNP56) and IS risk was initially identified via genome-wide association studies (GWAS), although the GWAS in different populations produced inconclusive results. Thus, we performed a meta-analysis to better explain the association between PDE4D SNP56 and IS r ...[more]

PMID: 27759733

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Project description:BACKGROUND: The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis. METHODS: Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 +/- 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index > or = 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect. RESULTS: In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index > or = 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index > or = 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27). CONCLUSIONS: The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.

Dataset Information

No Association Between Single-Nucleotide Polymorphism 56 (SNP56) in Phosphodiesterase 4D (PDE4D) Gene and Susceptibility to Ischemic Stroke: A Meta-Analysis of 15 Studies.

Publications

No Association Between Single-Nucleotide Polymorphism 56 (SNP56) in Phosphodiesterase 4D (PDE4D) Gene and Susceptibility to Ischemic Stroke: A Meta-Analysis of 15 Studies.

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