Oxidase P22phox C242T Polymorphism Research Articles

NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in diabetic patients: A meta-analysis

AimsPrevious studies suggested an association between C242T polymorphism in NADPH Oxidase p22phox and diabetic nephropathy (DN) risk, but the results were inconsistent. To obtain a more precise estimation, we carried out a meta-analysis to analyze the effect of C242T polymorphism in NADPH Oxidase p22phox on DN risk. MethodsWe searched PubMed, ISI Web of Science, and China National Knowledge Infrastructure for all eligible case–control studies through May 2016. The odds ratios (ORs), together with the 95% confidence intervals (CIs), were calculated to evaluate the strength of association between C242T SNP in NADPH Oxidase p22phox on DN risk. ResultsOverall, ten eligible studies involving a total of 1894 cases and 1746 controls were included in our meta-analysis. The results showed that there was no statistical evidence of association between NADPH oxidase p22phox C242T polymorphism and DN in all genetic models (T vs. C: OR 1.16, 95% CI 0.85–1.59, p=0.34; TT vs. CC: OR 1.49, 95% CI 0.80–2.76, p=0.21; TT/CT vs. CC: OR 1.18, 95% CI 0.81–1.72, p=0.40; TT vs. CT/CC: OR 1.31, 95% CI 0.82–2.11, p=0.26). However, significant association was found in diabetic patients with macroalbuminuria. ConclusionThis meta-analysis indicates that NADPH oxidase p22phox C242T polymorphism is associated with macroalbuminuria in diabetic patients. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous patients and well-matched controls are required.

NADPH oxidase p22phox C242T polymorphism and ischemic cerebrovascular disease: an updated meta-analysis.

BackgroundA growing number of studies on the associations between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox C242T polymorphism and risk of ischemic cerebrovascular disease have recently been published, but the results remain inconsistent.Material/MethodsWe performed an updated meta-analysis to evaluate this association. Eight case-control studies were included, involving 2045 cases and 2102 controls. Heterogeneity was assessed by the Q test and the I2 statistic. Begg and Egger’s tests were conducted to evaluate publication bias. Odds ratio (OR) was tested to identify the associations.ResultsSignificant associations between p22phox gene C242T polymorphism and ischemic cerebrovascular disease (ICVD) risk were observed in the allelic genetic model (OR=1.33, 95% confidence interval [CI] 1.00–1.77, p=0.048). No statistical significant association was found in the dominant model (OR=0.74, 95% CI 0.54–1.02, p=0.064) and recessive model (OR=1.40, 95% CI 0.89–2.19, p=0.146). Subgroup analysis showed an association in European populations for recessive model (OR=2.13, 95% CI 1.06–4.26, p=0.034) and no significant evidence of association in Asian populations was found (dominant model: OR=0.64, 95% CI 0.41–1.00, p=0.05; recessive model: OR=0.98, 95% CI 0.53–1.81, p=0.948; allelic model: OR=1.51, 95% CI 0.98–2.32, p=0.061).Conclusionsp22phox gene C242T polymorphism was associated with ICVD risk in the allelic genetic model, as well as in European populations for recessive model. No evidence showed association between p22phox gene C242T polymorphism and ICVD risk in the dominant model and recessive model. Furthermore, no association existed in Asian populations for any of the 3 genetic models and European populations in the dominant model and allelic model.

Investigation of association between donors' and recipients' NADPH oxidase p22phox C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients

BackgroundProduction of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22phox is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22phox and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied. MethodsOne hundred ninety six donor–recipient pairs were studied. The C242T polymorphism of p22phox was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation. ResultsThere was a significant association between the recipients' p22phox polymorphism and DGF occurrence (OR=2.5, CI: 1.2–4.9, p=0.0009). No significant association was detected between donors' p22phox polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=−12.8, CI: −22.9–12.8 (−22.9 to −2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22phox. ConclusionThese results suggest that the recipients' p22phox C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients.

Association between NADPH Oxidase p22phox C242T Polymorphism and Ischemic Cerebrovascular Disease: A Meta-Analysis

BackgroundEpidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox 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 FindingsSystematic 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 p22phox 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/SignificanceThis meta-analysis indicates that NADPH oxidase p22phox 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.

The effect of NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative damage in response to 8weeks aerobic exercise training.

The effect of NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative damage in response to 8weeks aerobic exercise training.

Effects of the NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative DNA damage in response to aerobic exercise training.

We examined the effects of the NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative DNA damage in response to acute and chronic exercises. One hundred three subjects were recruited, among which 26 healthy subjects (CC: 12, TC: 12, and TT: 2) were studied during rest, exercise at 85% VO(2)max, and recovery before and after 8 weeks of tread-mill running. Lymphocyte DNA damage increased significantly in response to exercise (p < 0.05). There were no significant differences in plasma MDA, SOD concentrations and lymphocyte DNA damage between CC genotype and T allele group, but significant endurance training differences were observed. Endurance training increased exercise time to exhaustion in both the CC genotype and T allele groups (p < 0.05) but no significant difference was found between groups. The results of the current study with young, healthy, Korean men are interpreted to mean that 1) the majority had the CC genotype of the NADPH oxidase p22phox C242T polymorphism (82.5%: CC, 15.5%: TC, 1.9%: TT), 2) acute exercise increased lymphocyte DNA damage, 3) endurance training significantly increased exercise time to exhaustion, and alleviated lymphocyte DNA damage, and 4) The NADPH oxidase p22phox C242T polymorphism, however, did not alter lymphocyte DNA damage or exercise performance at rest, immediately after exercise, or during recovery.

NAD (P) H oxidase p22 phox C242T polymorphism affects LDL particle size and insulin resistance in Japanese subjects.

Elevated cardiovascular risk is associated with an increased number of small, dense low-density lipoprotein (LDL) particles, which exhibit increased susceptibility to lipid oxidation, however, the mechanism determining LDL particle size has never been fully elucidated. We have examined the association between the C242T polymorphism of the p22 phox gene, which is a small subunit of vascular NAD(P)H oxidase, and both LDL particle size and clinical characteristics in 260 healthy subjects. Peak LDL particle diameter (LDL-PPD) was measured by continuous disk polyacrylamide gel electrophoresis. Twenty-one of the 217 subjects with the CC genotype showed pattern B (median LDL-PPD under 25.5 nm), whereas, none of the 43 subjects with TC + TT genotypes showed pattern B. The pattern B fraction was significantly larger in the CC group than in the TC + TT group (p = 0.030). The subjects with the CC genotype also showed a significantly higher fasting glucose level, plasma insulin level, and insulin resistance index of homeostasis model assessment (HOMA-R) than those with the TC + TT genotype. Our data demonstrate that variation in the small NAD(P)H oxidase subunit p22 phox gene substantially influences LDL particle size and may also reflect differences in the insulin sensitivity of non-diabetic subjects.