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Association between NADPH oxidase p22(phox) C242T polymorphism and ischemic cerebrovascular disease: a meta-analysis.

Li BH, Zhang LL, Zhang BB, Yin YW, Dai LM, Pi Y, Guo L, Gao CY, Fang CQ, Wang JZ, Li JC - PLoS ONE (2013)

Bottom Line: Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23).This meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke.However, this conclusion should be interpreted with caution due to the small sample size.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Yuzhong District, Chongqing, PR China.

ABSTRACT

Background: Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22(phox) C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methodology/principal findings: Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22(phox) C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93-1.26; additive model: OR = 1.33, 95%CI = 0.81-2.17; dominant model: OR = 1.00, 95%CI = 0.86-1.15; recessive model: OR = 1.06, 95%CI = 0.77-1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.

Conclusions/significance: This meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.

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Flow diagram of the selection of eligible studies.
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pone-0056478-g001: Flow diagram of the selection of eligible studies.

Mentions: The present study met the PRISMA statement requirements (Appendix S2) and MOOSE guidelines (Appendix S3). The study selection process is detailed in Figure 1. Based on our preliminary search criteria, a total of nine publications were eligible [24], [26]–[30], [40]–[42]. Among these articles, one study was review article [40]. Two studies reported the p47phox C923T rather than p22phox C242T polymorphism [41], [42]. Hence, six studies were included in the final meta-analysis, including 1,948 cases and 2,357 controls. Khan et al. provided no frequency of C242T polymorphism in cases and controls, and we failed to obtain these data by contacting the corresponding author, which limited our calculation of OR and 95%CI for allelic model and additive model. All studies were case-control in design. Table 1 shows the studies identified and their main characteristics. The NOS results showed that the average score was 8.5 (range 8 to 9), indicating that the methodological quality was generally good. Statistical powers based on the given sample size of each study ranged from 5.1% to 70.8%, which were all lower than 80%. Among the six articles, three focused on Asians, and three on Europeans. The countries of these studies included Japan, UK, Germany and Poland. Five studies characterized ischemic stroke subtypes in their analyses, allowing subtype specific meta-analysis. However, because of the limited available data on cardioembolic, other determined etiology and undetermined subtypes, we only made meta-analysis for small-vessel occlusive ischemic stroke and large-artery atherosclerotic ischemic stroke, in which five studies were combined for small-vessel occlusive subtype [24], [26]–[29] and four for large-artery atherosclerotic subtype [24], [26]–[28].


Association between NADPH oxidase p22(phox) C242T polymorphism and ischemic cerebrovascular disease: a meta-analysis.

Li BH, Zhang LL, Zhang BB, Yin YW, Dai LM, Pi Y, Guo L, Gao CY, Fang CQ, Wang JZ, Li JC - PLoS ONE (2013)

Flow diagram of the selection of eligible studies.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569432&req=5

pone-0056478-g001: Flow diagram of the selection of eligible studies.
Mentions: The present study met the PRISMA statement requirements (Appendix S2) and MOOSE guidelines (Appendix S3). The study selection process is detailed in Figure 1. Based on our preliminary search criteria, a total of nine publications were eligible [24], [26]–[30], [40]–[42]. Among these articles, one study was review article [40]. Two studies reported the p47phox C923T rather than p22phox C242T polymorphism [41], [42]. Hence, six studies were included in the final meta-analysis, including 1,948 cases and 2,357 controls. Khan et al. provided no frequency of C242T polymorphism in cases and controls, and we failed to obtain these data by contacting the corresponding author, which limited our calculation of OR and 95%CI for allelic model and additive model. All studies were case-control in design. Table 1 shows the studies identified and their main characteristics. The NOS results showed that the average score was 8.5 (range 8 to 9), indicating that the methodological quality was generally good. Statistical powers based on the given sample size of each study ranged from 5.1% to 70.8%, which were all lower than 80%. Among the six articles, three focused on Asians, and three on Europeans. The countries of these studies included Japan, UK, Germany and Poland. Five studies characterized ischemic stroke subtypes in their analyses, allowing subtype specific meta-analysis. However, because of the limited available data on cardioembolic, other determined etiology and undetermined subtypes, we only made meta-analysis for small-vessel occlusive ischemic stroke and large-artery atherosclerotic ischemic stroke, in which five studies were combined for small-vessel occlusive subtype [24], [26]–[29] and four for large-artery atherosclerotic subtype [24], [26]–[28].

Bottom Line: Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23).This meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke.However, this conclusion should be interpreted with caution due to the small sample size.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Yuzhong District, Chongqing, PR China.

ABSTRACT

Background: Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22(phox) C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies.

Methodology/principal findings: Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22(phox) C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93-1.26; additive model: OR = 1.33, 95%CI = 0.81-2.17; dominant model: OR = 1.00, 95%CI = 0.86-1.15; recessive model: OR = 1.06, 95%CI = 0.77-1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%.

Conclusions/significance: This meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.

Show MeSH
Related in: MedlinePlus