Phosphodiesterase 4D Gene Polymorphisms Research Articles

Phosphodiesterase 4 D(PDE4D) gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis.

Studies on the relationship between Phosphodiesterase 4 D (PDE4D) gene polymorphism with the risk of ischemic stroke (IS) have shown discordant results. The present meta-analysis was aimed to clarify the relationship between PDE4D gene polymorphism with the risk of IS by estimating pooled analysis of published epidemiological studies. A comprehensive literature search for all the published articles was performed in various electronic databases, including PubMed, EMbase, Cochrane Library, Trip Database, Worldwide Science, CINAHL, and Google Scholar up to 22nd December 2021. Pooled Odds ratios (ORs) with 95% Confidence Intervals (CIs) under dominant, recessive, and allelic models were calculated. Subgroup analysis based on ethnicity (Caucasian vs. Asian) was performed to examine the reliability of these findings. Sensitivity analysis was also performed to detect the heterogeneity between studies. Finally, Begg's funnel plot was used to assess the potential for publication bias. In our meta-analysis, we identified a total of 47 case-control studies with 20,644 ischemic stroke (IS) cases and 23,201 control subjects, including 17 studies of Caucasian descent and 30 studies of Asian descent. Our findings suggest that there was a significant relationship between SNP45 gene polymorphism and risk of IS (Recessive model: OR = 2.06, 95% CI 1.31-3.23), SNP83 overall (allelic model: OR = 1.22, 95% CI 1.04-1.42), Asian (allelic model: OR = 1.20, 95% CI 1.05-1.37), and SNP89 Asian (Dominant model: OR = 1.43, 95% CI 1.29-1.59, recessive model: OR = 1.42, 95% CI 1.28-1.58) respectively. However, no significant relationship was found between SNP32, SNP41, SNP26, SNP56, and SNP87 gene polymorphisms and risk of IS. Findings of this meta-analysis conclude that SNP45, SNP83, and SNP89 polymorphism could be capable of increasing stroke susceptibility in Asians but not in the Caucasian population. Genotyping of SNP 45, 83, 89 polymorphisms may be used as a predictor for the occurrence of IS.

The relationship between phosphodiesterase 4D gene polymorphism and coronary heart disease.

Coronary atherosclerotic heart disease is one of the most common heart diseases that seriously endanger human health. The study found that intracellular second messenger CAMP plays an important role in inhibiting the proliferation and migration of vascular smooth muscle and the local inflammatory response at the damaged vessel. Phosphodiesterase 4D (PDE4D) can specifically degrade cAMP. The purpose of this article is to investigate the relationship between phosphodiesterase 4D gene polymorphism and coronary heart disease and the effect of phosphodiesterase 4D gene polymorphism on cardiovascular, using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used to detect 50 patients with coronary heart disease (ACS group) and 100 patients who were diagnosed with coronary artery disease by coronary angiography at the same time as the control group (NC group). The results of the study showed that the frequencies of AA, AG, and GG genotypes in 150 samples were 25.67%, 54.66%, and 22.67%, respectively, which was consistent with Hard Weber's law (X = 2.186, P = 0.101). The distribution of GG genotype (18% vs. 27%), AA + AG genotype (85% vs. 74%), G (57% vs. 55%), A (43% vs. 45 %) There was no statistically significant difference in allele frequency (P <0.05). From this, it can be seen that the rs918592 polymorphism of the PDE4D gene is not associated with coronary heart disease.

Interaction between CONNEXIN37 and PDE4D gene polymorphisms with susceptibility to ischemic stroke in Chinese population.

The objective of this study was to test the relationship of several single nucleotide polymorphisms (SNPs) within phosphodiesterase 4D ( PDE4D) and connexin 37 ( CONNEXIN37) gene additional interactions with ischemic stroke (IS) risk. The online software SNPstats was used for Hardy–Weinberg equilibrium testing. Generalized multifactor dimensionality reduction (GMDR) was employed to detect the potential interactions among CONNEXIN37 gene, PDE4D gene, and smoking. The results indicated that the rs1764391-T and rs966221-G were correlated with higher IS risk, the corresponding ORs (95% CI) were 1.66 (1.21–2.03) and 1.48 (1.11–1.92), respectively. We also found that the first two loci including rs1764391 and rs918592, and the other two-loci including rs1764391 and smoking were significant in the GMDR model. Participants with rs1764391-CT/TT and rs918592-CT/TT genotype have the highest IS risk, compared to subjects with rs1764391-CC and rs918592-CC genotype, OR (95%CI) = 3.16 (1.83–4.45); smokers with rs1764391-CT/TT genotype also have the highest IS risk, compared to never smokers with rs1764391-CC genotype, OR (95%CI) = 2.82 (1.53–4.15), but no significant interaction combinations were found between gene and alcohol drinking. So in this study, the rs1764391-T and rs966221-G, rs1764391–rs918592 interaction, rs1764391–smoking interaction were all associated with higher IS susceptibility. Impact statement Till now, no study investigated the interaction between CONNEXIN37 and PDE4D gene, and the gene–environment interaction. Therefore, in the current study, we aimed to evaluate the impact of interactions between CONNEXIN37 and PDE4D gene, and its interaction with environmental risk factors on susceptibility to ischemic stroke (IS).

Relationship of phosphodiesterase 4D (PDE4D) gene polymorphisms with risk of ischemic stroke: a hospital based case-control study

Background: Stroke remains a leading cause of death and disability worldwide. Ischemic stroke (IS) accounts for around 80–85% of total stroke and is a complex polygenic multi-factorial disorder which is affected by a complex combination of vascular, environmental, and genetic factors.Objective: The study was conducted with an aim to examine the relationship of single nucleotide polymorphisms (SNPs) of PDE4D (T83C, C87T, and C45T) gene with increasing risk of IS in patients in North Indian population.Methods: In this hospital-based case-control study, 250 IS subjects and 250 age-and sex-matched control subjects were enrolled from the Neurosciences Centre, A.I.I.M.S., New Delhi, India. Deoxyribonucleic acids (DNAs) were extracted using the conventional Phenol–Chloroform isolation method. Different genotypes were determined by Polymerase chain reaction– Restriction fragment length polymorphism method. Odds ratio (OR) and 95% Confidence Interval (CI) of relationship of polymorphisms with risk of IS were calculated by conditional multivariable regression analysis.Results: High blood pressure, low socioeconomic status, dyslipidemia, diabetes, and family history of stroke were observed to be statistically significant risk factors for IS. Multivariable adjusted analysis demonstrated a statistically significant relationship between SNP 83 of PDE4D gene polymorphism and increasing odds of IS under the dominant model of inheritance (OR, 1.59; 95% CI, 1.02 to 2.50; p value = 0.04) after adjustment of potential confounding variables. Stratified analysis on the basis of TOAST classification demonstrated a statistically significant association for increasing 2.73 times odds for developing large vessel disease stroke as compared to controls (OR, 2.73; 95% CI, 1.16 to 0.02; p value = 0.02). We did not find any significant association of SNPs (C87T and C45T) of the PDE4D gene with the risk of IS.Conclusion: SNP 83 of PDE4D gene may increase the risk for developing IS whereas SNP 87 and SNP45 of PDE4D may not be associated with the risk of IS in the North Indian population. Prospective cohort studies are required to corroborate these findings.

A meta-analysis of PDE-gene polymorphism and cerebral infarction risk.

Previous studies identified that phosphodiesterase 4D (PDE4D) gene polymorphism might be associated with cerebral infarction or ischemic stroke, and hemorrhagic stroke in human populations. However, as yet, no meta-analysis has revealed any detailed association. We retrospectively reviewed studies regarding the relationship of PDE4D gene polymorphism with ischemic stroke (IS) published during the period January 2003 to September 2012. According to the inclusion criteria, 9 of 105 initial studies were included in the subsequent analysis. The PubMed, Embase and CNKI of China were searched to identify the relevant studies. A total of 186 young patients with IS were included for the meta-analysis and 232 matched control subjects were enrolled and results were presented. The association of PDE4D gene polymorphism with IS in various populations was examined. The results suggested that single nucleotide polymorphism (SNP), SNP 83 in PDE4D gene was significantly related with susceptibility to IS. The meta-analysis also showed that PDE4D gene was associated with an enhanced risk of IS. The meta-analysis suggested that PDE4D SNP 87 constitutes an independent risk factor for IS development. To the best of our knowledge, the present meta-analysis reveals a number of possible associations between PDE4D gene polymorphism and IS.

Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95% confidence interval=1.46-11.18) (p=0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p=0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p=0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

Genetic variants of phosphodiesterase 4D gene are associated with an enhanced risk for ischemic stroke in young Chinese population

Previous studies have shown that the phosphodiesterase 4D (PDE4D) gene is a susceptibility gene for ischemic stroke (IS) primarily in elder populations. However, few studies have reported the role of the PDE4D gene polymorphisms in a young cohort. To investigate the association between the PDE4D gene polymorphisms and young-onset IS in Chinese population. A total of 186 young patients (18-45 years) with IS and 232 matched control subjects were recruited. Two SNPs (rs918592 and rs2910829) in PDE4D gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio and 95% confidence intervals (95% CI) were calculated to test the association between the genetic factors and IS. The rs918592A/A genotype frequency and A allele frequency, rs2910829 CT/TT genotype frequency and T allele frequency of young IS group were significantly higher than those of the control group ( P < 0.05). Besides, the frequency of Hap (A-T) was remarkably higher in the young patients than that in the controls (OR =4.047, 95% CI: 3.521-4.652). Hap (A-C) and Hap (G-C) were associated with decreased risk of IS (OR =0.640, 95% CI: 0.452-0.906; OR =0.675, 95% CI: 0.466-0.978, respectively). Our findings suggest that the rs918592 and rs2910829 polymorphisms and haplotypes of PDE4D gene are significantly associated with IS in Chinese young population.

Phosphodiesterase 4D (PDE4D) gene polymorphism in patients with acute stroke from Moscow

Two PDE4D gene polymorphisms [SNP41 (rs152312 and SNP87 (rs 2910829)] were studied in patients with acute stroke (n = 577) and in control sample (n = 270). Significant differences in the genotype and allele frequency distribution were found between these samples for polymorphism SNP41. We showed that the AA and AG genotypes of SNP41 polymorphism were associated with higher risk of acute stroke development in the Moscow population (OR = 1.6). No association of SNP87 polymorphism with the disease was observed.

Phosphodiesterase 4D (PDE4D) Gene Variants and Risk of Ischemic Stroke in the Taiwanese Population

Objectives: It has been suggested that genetic variants in the phosphodiesterase 4D (PDE4D) gene confer risk of ischemic stroke. However, the cerebral infarction/cerebral hemorrhage ratio is lower in Asian populations compared with those in Caucasian and black populations. Thus, the association between variations in the PDE4D gene and ischemic stroke in Taiwan needs to be replicated. In the present study, we evaluated whether the PDE4D gene polymorphism confers a risk of ischemic stoke in Taiwanese patients. Methods: Two single-nucleotide polymorphisms (SNPs) covering the PDE4D gene were genotyped using genomic DNA sequencing and a high-throughput TaqMan PCR assay in 100 patients who had suffered an ischemic stroke and 270 healthy individuals. Results: No significant associations with ischemic stroke were observed with the SNP87 (rs2910829) or SNP41 (rs152312) SNPs from PDE4D, which were a part of the Icelandic at-risk haplotypes. Conclusions: The present data does not support a significant role for PDE4D polymorphisms in genetic susceptibility to ischemic stroke in the Taiwanese population.

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

It has been reported that the variants of the PDE4D (phosphodiesterase 4D) gene are associated with stroke, especially with the combination of cardio-embolic and carotid stroke in the Icelandic population, but it is still very controversial as to whether PDE4D is a susceptible gene for stroke in other populations. In the present study, we tested whether the PDE4D gene variation also confers stroke risk in a Chinese population. Our hypothesis was tested in a case-control study of a Chinese population comprising 639 stroke patients (including 253 with cerebral thrombosis, 171 with lacunar infarction and 215 with intracerebral haemorrhage) and 887 healthy controls. Three SNPs (single nucleotide polymorphisms) (rs966221, rs456009 and rs2910829) in PDE4D were chosen based on the significant association with stroke reported previously in a Western population, and these were genotyped using PCR/RFLP (restriction-fragment-length polymorphism) and confirmed by sequencing. We found that only SNP83 (rs966221) was associated with stroke. Allele C of rs966221 is a risk allele, conferring an increased risk for atherothrombotic strokes [OR (odds ratio), 1.51; 95% CI (confidence interval), 1.09-2.10] independent of conventional risk factors. Haplotype analysis confirmed that haplotype G-C-C was associated with increased risk for atherothrombotic stroke (OR, 1.80; 95% CI, 1.300-2.491). Our findings support that SNP83 of PDE4D is a genetic risk factor for atherothrombotic strokes in a Chinese population.