Association Between Angiotensin-Converting Enzyme Gene I/D Polymorphism and Polycystic Ovary Syndrome Susceptibility: a Meta-analysis.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

MMP-10 rs17435959 Polymorphism is Associated with the Formation and Stability of Carotid Atherosclerosis Plaque: A Case-Control Study.

BACKGROUND: Matrix metalloproteinase 10 (MMP-10) has a close relationship with carotid atherosclerosis (CAS) and cerebral infarction. The MMP-10 rs17435959 polymorphism causes a leucine to valine transition at codon 4 in exon 1 of the MMP-10 gene and may have functional effects. OBJECTIVES: To investigate the relationship between the MMP-10 rs17435959 polymorphism and the formation and stability of CAS plaques. MATERIALS AND METHODS: The present case-control study contains 738 visitors who came to our health examination center for the first time. According to the carotid ultrasound examinations, visitors were classified into the vulnerable plaque group (41-86 years old, 141 male, 105 female), the stable plaque group (41-86 years old, 141 male, 105 female) and the no plaque group (41-85 years old, 141 male, 105 female). All visitors in the three groups were sex- and- age-matched, and cardiovascular and cerebrovascular diseases were absent. The polymorphism was genotyped by real-time polymerase chain reaction- restriction. RESULTS: Compared to the GG genotype, the frequency of the CC and CG genotypes was significantly more common in the vulnerable plaque group than in the no plaque group (18.7% vs. 7.7%, unadjusted P = 0.002). Moreover, compared to the G allele, the frequency of the C allele was significantly more common in the vulnerable plaque group than in the no plaque group (10.4% vs. 3.9%, unadjusted P = 0.000) and in the vulnerable plaque group than in the stable plaque group (10.4% vs. 5.1%, unadjusted P = 0.008). Binary logistic regression showed that the CC and CG genotype was independent risk factor for the formation (P = 0.019, OR = 1.961, 95% CI [1.117, 3.444]) and vulnerability (P = 0.035, OR = 1.842, 95% CI [1.045, 3.247]) of CAS plaques. Moreover, individuals who have the C allele showed a higher level of fibrinogen, which was an independent risk factor for the formation of CAS plaques (P = 0.000, OR = 2.425, 95% CI [1.475, 3.985]). CONCLUSIONS: The rs17435959 polymorphism was associated with the formation and vulnerability of CAS plaques. Individuals who had variant-type MMP-10 showed higher levels of fibrinogen, which promoted the formation of CAS plaques.

An experimental study on the use of a sequencing-batch membrane bioreactor (SBMBR) for the treatment of mixed municipal wastewater.

Several water treatment techniques have been combined using the sequencing batch reactor with the membrane bioreactor for addressing water pollution. However, cleaning of the membrane is dependent on the approach involved as well as the operating conditions. In the present study, the sequencing-batch membrane bioreactor was used to treat real mixed municipal wastewater. The pollutant removal and membrane filtration performances were examined. The results show that the average removal rates of chemical oxygen demand (COD), total nitrogen, NH3-N, total phosphorus, and turbidity were 90.75, 63.52, 92.85, 87.58, and 99.48%, respectively, when the system was in continuous operation for 95 days. The membrane had a significant effect on COD and turbidity removal and provided stable performances for nitrogen and phosphorus removal. By observing the appearance of the membrane modules before and after the cleaning operation, it was concluded that the deposited sludge and granular sediment on the membrane surface can be effectively removed by hydraulic cleaning. In addition, recovery of membrane filtration performance to 60% of that of a new membrane can be achieved. Furthermore, we found that different sequences and duration of cleaning have different effects on the recovery of membrane filtration performance.

[Association between -1296T/C and -915A/G polymorphisms of matrix metalloproteinase inhibitor-3 gene and atherosclerotic cerebral infarction in an ethnic Han Chinese population].

OBJECTIVE: To assess the association between -1296T/C and -915A/G polymorphisms in the promoter region of matrix metalloproteinase inhibitor-3 gene (TIMP-3) and atherosclerotic cerebral infarction in an ethnic Han Chinese population. METHODS: Peripheral blood samples were collected from 485 patients with atherosclerotic cerebral infarction and 525 healthy controls. Serum levels of TIMP-3 were measured with an enzyme-linked immunosorbent assay (ELISA). The polymorphisms of the TIMP-3 gene were analyzed with DNA sequencing. RESULTS: There were significant differences in genotype and allele frequencies in -1296T/C and -915A/G between the patients and healthy controls (chi-square: 5.227 and 5.869; P: 0.022 and 0.015, respectively). Besides, there was a strong linkage disequilibrium between -1296T/C and -915A/G (D'=1.0, r(2)=0.991). The serum levels of TIMP-3 in patients were significantly higher than the control group [(248.90 ± 97.10) pg/mL vs. (200.17 ± 79.70) pg/mL, t=2.098, P=0.039]. CONCLUSION: The -1296T/C and -915A/G polymorphisms of the TIMP-3 gene are associated with increased risk for atherosclerotic cerebral infarction in ethnic Han Chinese and may be used as molecular markers for the disease. There is also strong linkage disequilibrium between the two loci.

[Association of MMP-14 gene polymorphism with cerebral infarction - a case-control study].

OBJECTIVE: To investigate the association between cerebral infarction (CI) and single nucleotide polymorphism (SNP) in the exon of membrane-type 1 matrix metalloproteinase (MMP-14) gene in Chinese Han population. METHODS: Five hundred seventy four patients with CI and 463 healthy individuals were recruited. Serum MMP-14 level was measured with enzyme-linked immunosorbent assay (ELISA). rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a TaqMan assay. Multivariate logistic regression was carried out to analyze the risk factors of CI. RESULTS: A significant lower risk of CI was found in individuals with MMP-14 rs2236307 TC and CC genotypes (vs. TT genotype: P<0.05). The frequencies of MMP-14 rs2236307 C allele were significantly different between the CI group (37.46%) and the control group (43.95%) (P=0.003). Serum level of MMP-14 was higher in the CI group (P=0.003) and was also higher in the group with MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes (P=0.000; P=0.009). Logistic regression analysis indicated that the MMP-14 rs2236307 CT+CC genotypes was a protective factor, and that history of hypertension, smoking status, triglycerides, diastolic blood pressure and systolic blood pressure were the independent risk factors of CI (AOR:2.027, 1.302, 1.296, 1.434, 2.087; P<0.05). CONCLUSION: The rs2236307 polymorphism of MMP-14 gene is associated with CI, for which the C allele maybe a protective factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been found.

Celastrol may have an anti-atherosclerosis effect in a rabbit experimental carotid atherosclerosis model.

BACKGROUND: Celastrol may have an anti-atherosclerosis effect. This study aimed to investigate if celastrol had an anti-AS effect using a rabbit experimental carotid atherosclerosis model. METHODS: Forty male Japanese white rabbits were divided into the sham group (normal diet), the model group (high fat diet), the group treated with celastrol (high fat diet) and the group treated with atorvastatin (high fat diet) randomly. The rabbits fed a high fat diet underwent balloon injury of the right common carotid artery and were treated with dimethyl sulfoxide (DMSO) (the model group, 3.5 ml/kg/d), celastrol and its dissolvent DMSO (the celastrol group, 1 mg/kg/d and 3.5 ml/kg/d) and atorvastatin and its dissolvent DMSO (the atorvastatin group, 2.5 mg/kg/d and 3.5 ml/kg/d) for 12 weeks by gavage. RESULTS: The ratio of the plaque area and the arterial wall cross-section area in the celastrol group was significantly less than the model group (P < 0.001), and there was no significant difference compared with the atorvastatin group. The serum level of LDL-C of the celastrol group was significantly lower than the model group (P = 0.014), and there was no significant difference compared with the atorvastatin group. The expression of VEGF in the celastrol group was significantly less compared with the model group (P = 0.014), whereas the expression of VEGF in the atorvastatin group and the model group showed no significant differences. CONCLUSION: Our findings suggest that celastrol effectively reduced the plaque ratio, decreased the serum levels of LDL and downregulated the expression of VEGF, suggesting an anti-AS effect of celastrol.

Interleukin-1α -899 (+4845) C→T polymorphism is not associated with aggressive periodontitis susceptibility: A meta-analysis based on 19 case-control studies.

A number of published studies investigated the association between interleukin-1α (IL-1α) -899 (+4845) C→T polymorphism and susceptibility to aggressive periodontitis (AgP). However, the results from different studies are controversial. This study was conducted to further investigate the association between IL-1α -899 (+4845) C→T polymorphism and AgP using a meta-analysis. A search was conducted through PubMed up to May 1, 2013 and a total of 19 relevant case-control studies were identified. The results of this meta-analysis demonstrated that IL-1α -899 (+4845) C→T polymorphism is not associated with susceptibility to AgP under allele T vs. C [odds ratio (OR)=1.00, 95% confidence interval (CI): 0.88-1.14, P=0.98; I2=28.86%] or allele A vs. C comparison (OR=0.99, 95% CI: 0.85-1.14, P=0.85; I2=33.66%). The subgroup analyses based on ethnicity, source of controls and Hardy-Weinberg equilibrium (HWE) also revealed no such association. There existed a weak publication bias (Egger's test P=0.02). In conclusion, based on the currently available evidence, there is no association between IL-1α -899 (+4845) C→T polymorphism and susceptibility to AgP.

Positive association of MMP 14 gene polymorphism with vulnerable carotid plaque formation in a Han Chinese population.

BACKGROUND: MMP 14 is expressed in atherosclerotic plaques and potentially plays an important role in the development of vulnerable carotid plaques. MMP 14 gene polymorphisms can influence the bioactivity or expression of MMP 14. OBJECTIVE: The aim of this study was to investigate the association between MMP 14 position + 7096 T > C (NM_004995.2:c.855T> C, rs2236307) polymorphism and vulnerable carotid plaque formation. METHODS: 1370 patients with ischemic cerebral infarctions were enrolled and divided into three groups according to their carotid ultrasound examination: No plaque group (n = 346), stable plaque group (n = 695) and vulnerable plaque group (n = 329). The traditional atherosclerosis risk factors were recorded, and the MMP 14 polymorphism were genotyped by Applied Biosystems 7300 Real-Time PCR System using the TaqMan assay. RESULTS: In the multiple logistic regression analysis done among the sub-groups, compared to no carotid plaque group, individuals with the MMP 14 position + 7096 TC+ CC genotype showed a significantly (p = 0.009) lower risk for vulnerable plaque (AOR = 0.675; 95% CI, 0.568-0.922) formation compared with subjects of the TT genotype; however, no relation between TC+ CC genotype and stable carotid plaque was observed (p > 0.125). Age was a risk factor for both stable plaque (p = 0.000; AOR = 3.732; 95% CI: 2.496-5.58) and vulnerable plaque formation (p = 0.001; AOR = 2.234; 95% CI: 1.387-3.597). Meanwhile, fibrinogen (> 4.0 g/L) was a risk factor for stable plaque (p = 0.004; AOR = 2.313; 95% CI: 1.308-4.091). CONCLUSIONS: The MMP 14 position + 7096 TC+ CC genotype might lower the risk of vulnerable carotid plaque formation. Fibrinogen (> 4.0 g/L) was a risk factor for stable plaque.

[Association between matrix metalloproteinase-10 gene polymorphisms and instability of carotid plaque].

OBJECTIVE: To assess the association between 2 single nucleotide polymorphisms (SNPs) located in exonic regions of matrix metalloproteinase-10 (MMP-10) gene and instability of carotid plaques in a Han Chinese population. METHODS: Five hundred and eighty-five patients were divided into carotid vulnerable plaque group (n=206) and stable plaque group (n=379) based on results of carotid B-mode ultrasonography. The SNPs were genotyped by real-time polymerase chain reaction using an ABI 7300 TaqMan platform. RESULTS: The distribution of rs17435959 between the two groups was significantly different at both genotypic (GC+CC vs. GG, P=0.006, OR=2.012) and allelic levels (C vs. G, P=0.001,OR=2.160). Above differences have remained significant with binary logistic regression analysis (P=0.007, OR=2.022; P=0.002, OR=2.104). The minor allele frequency of rs17293607 was 0.56%. CONCLUSION: Above findings suggested that rs17435959 of the MMP-10 gene is associated with carotid vulnerable plaque in ethnic Chinese Hans. The C allele may be a susceptible predictor for carotid vulnerable plaque.

Matrix metalloproteinase 10 gene polymorphism and atherothrombotic cerebral infarction risk in a Han Chinese population.

BACKGROUND: Matrix metalloproteinase 10 (MMP10) plays an important role in ischemic stroke and has a close relationship with some stroke risk factors. The aim of this study was to investigate the relationship between two single nucleotide polymorphisms (SNP) in the exon regions of the MMP10 gene and atherothrombotic cerebral infarction risk. METHODS: Five hundred and thirty-seven hospital-based patients who had suffered first atherothrombotic cerebral infarction and 580 unrelated healthy controls were enrolled. Demographic and clinical features of the subjects were recorded, and two polymorphisms, rs17435959 (G>C), rs17293607 (C>T) were chosen to be genotyped by real-time polymerase chain reaction-restriction TaqMan probes using the ABI 7300 TaqMan platform. RESULTS: There were several clinical parameters, such as blood pressure, fasting blood glucose, total cholesterol, homocysteine, as well as carotid plaque and smoking, but not average age and sex ratios that showed significant differences between patients and control subjects. For rs17435959, there was no significant difference between the ischemic stroke group and the healthy control group in genotype frequency (OR=1.295, P=0.187, 95% CI (0.882-1.899)) or allele frequency (OR=1.267, P=0.202, 95% CI (0.881-1.823)). Moreover, in smoking, none smoking, having carotid plaque, no carotid plaque, male or female subtypes, there was significant difference between patients and control subjects in genotype frequencies or allele frequencies. The minor allele frequency of rs17293607 was 0.92%, prohibiting further study of this allele. CONCLUSIONS: These findings suggest that the rs17435959 SNP may not associated with atherothrombotic cerebral infarction risk. We also found that rs17293607 is not polymorphic in our study population.

Lack of independent relationship between the MMP-12 gene polymorphism and carotid plaque susceptibility in the Chinese Han population.

The purpose of this study was to investigate whether a polymorphism in the matrix metalloproteinase-12 gene (MMP-12 -82A/G) is correlated with serum protein levels or with the susceptibility for carotid plaques in the Chinese Han population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the -82A/G polymorphism in the MMP-12 gene for 1314 patients with acute cerebral infarctions; 710 of these cases were diagnosed with stable plaques, 340 cases were diagnosed with vulnerable plaques and 264 cases had no plaques. At the same time, serum MMP-12 levels were measured using the enzyme-linked immunosorbent assay (ELISA). Compared to the AA genotype, the frequency of the AG+GG genotypes was not significantly different between the three groups (χ(2) = 1.242, p = 0.537), and the frequency of the G allele of the MMP-12 gene was not different within the three subgroups (χ(2) = 1.218, p = 0.544). There were no significant differences in MMP-12 protein levels among the three groups (F = 0.675, p = 0.510); similarly, there was no difference in MMP-12 protein levels between the stable plaque group and the vulnerable plaque group (p = 0.755). There was also no difference between the vulnerable plaque group and the no plaque group (p = 0.420). The current data suggest that the inter-individual variability in the MMP-12 gene variation may not be a risk factor for vulnerable plaques in the Chinese Han population.

[Association between matrix metalloproteinase-8 -799C/T polymorphism and instability of carotid plaque].

OBJECTIVE: To investigate the association between a -799C/T polymorphism in the promotor region of matrix metalloproteinase-8 (MMP-8) gene and instability of carotid plaque in Chinese Han population. METHODS: A total of 451 acute infarction patients from the Department of Neurology of Taizhou Hospital were divided into carotid vulnerable plaque group and carotid stable plaque group according to the results of carotid B-mode ultrasonography. Serum MMP -8 level was measured by the means of enzyme-linked immunosorbent assay (ELISA). At the same time, the MMP-8 -799C/T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum level of MMP-8 in the carotid vulnerable plaque group was higher than that in the carotid stable plaque group (t= 2.894, P= 0.004). The genotype distribution of -799C/T polymorphism between the two groups was significantly different (Chi-square = 13.65, P= 0.000). Serum level of MMP-8 in patients with TT genotype was higher than that in patients with CC genotype (t= 3.141, P= 0.001). CONCLUSION: The present study suggested that serum level of MMP-8 and the -799C/T polymorphism of MMP-8 gene are associated with carotid vulnerable plaque in Chinese Han population, and the T allele may be a predictor for the susceptibility of carotid vulnerable plaque.

Genotype association of C(-735)T polymorphism of the MMP-2 gene with the risk of carotid atherosclerosis-vulnerable plaque in the Han Chinese population.

The aim of the current study was to explore the possible association of the polymorphism of C(-735)T in MMP-2 with the vulnerable plaque risk in ultrasound-confirmed carotid atherosclerosis cases. Serum MMP-2 levels were measured to investigate the relationship between the MMP-2 level and the genetic variability. The MMP-2 polymorphism was detected by PCR-RFLP in the 243 cases with stable plaque and 221 cases with vulnerable plaque. Serum MMP-2 levels were measured with ELISA. The results showed that MMP-2 was significantly higher in the cases with vulnerable plaque than in the cases with stable plaque. A statistical difference was found between the genotype distributions in the vulnerable plaque cases and that in the stable cases. T-allele frequency was also found to be over-represented in the stable plaque cases than in the vulnerable plaque cases, which might partially explain the observed difference in the serum MMP-2 levels in the different plaque cases. The current results also suggested that MMP-2 was a risk factor in the cases with vulnerable plaques, whereas TT genotype and T allele might be protective factors in the cases with vulnerable plaques.