Objective To explore whether the polymorphism of transforming growth factor β1 (TGF β1) gene at 869T/C and 915G/C loci contributes to the genetic susceptibility to hypertension. Methods Assessed under the same criteria, all case control studies on relationship between the polymorphism of TGF β1 gene and hypertension were searched in both English and Chinese databases. All articles retrieved were screened and evaluated, and meta-analyses were conducted with RevMan 5.1 software. Results A total of 14 case control studies were included. The results of meta-analyses showed TGF β1 gene C allele was related to hypertension (OR=1.37, 95%CI 1.21 to 1.54). It was noted that individuals with CC genotype and TT genotype had a significant increased risk of hypertension (OR=1.43, 95%CI 1.27 to 1.60; OR=0.64, 95%CI 0.53 to 0.78, respectively). And there was no b evidence showing that TGF β1 915G/C genetic polymorphism was related to hypertension. The results from meta-analyses of the studies based on Chinese population on the two loci were in consistent with the outcomes of overall meta-analyses. Sensitivity analyses indicated the results were stable. And publication bias was not present, reflected by P values from Egger’s regression asymmetry test and Begg’s adjusted rank correction test. Conclusions 869T/C polymorphism of TGF β1 gene is associated with hypertension. C allele is potentially one of the genetic risk factors for hypertension. Present studies do not support a direct relationship between 915G/C polymorphism TGF β1 gene and hypertension.
Objective To investigate the influence of CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms on warfarin dosages of patients after heart valve replacement. Methods A total of 133 patients undergoing heart valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital from November 2011 to August 2012 were included in this study. Polymerase chain reaction（PCR）gene sequencing was performed to detect CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphism of these 133 patients. Patients were grouped according to their genotypes，and average warfarin dosages were compared between different genotype groups. Results The frequencies of CYP2C9 3 AA，AC and CC were 127 patients，6 patients and 0 patient respectively，and average daily warfarin dosages were 3.75 mg and 2.13 mg respectively which were statistically different between differentCYP2C9 3 genotypes （P＜0.05）. The frequencies of VKORC1-1639 G＞A GG，GA and AA were 3 patients，32 patientsand 98 patients respectively，and average daily warfarin dosages were 6.00 mg，4.50 mg and 3.00 mg respectively which were statistically different between different VKORC1-1639 G＞A genotypes （P＜0.05）. The frequencies of CYP4F2 rs 2108622 CC，CT and TT were 67 patients，59 patients and 7 patients respectively，and average daily warfarin dosages were 3.00 mg，3.75 mg and 4.50 mg respectively which were statistically different between different CYP4F2 rs2108622 genotypes（P＜0.05）. Conclusion CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms are associated with individual difference of warfarin dosages of patients after heart valve replacement.
Objective To systematically evaluate anti-platelet effect of clopidogrel influenced by CYP2C192,3 polymorphism in patients with cardiovascular diseases, in order to provide references for its safe medication. Methods Literature was retrieved in electronic databases covering EMbase, PubMed, The Cochrane Library, CBM and CNKI from establishment dates to November, 2011. Observational studies and clinical trials were included, cross-checked, assessed and pooled for meta-analysis. meta-analysis was performed using the software RevMan 5.1. Results A total of 13 articles including 14 trials (n=36 855) were included. The results of meta-analysis showed that: a) there was no significant difference in the incidences of cardiovascular events between CYP2C192,3 carriers and CYP2C191 carriers; b) the risk of stent thrombosis in CYP2C192,3 carriers was significantly higher than that in CYP2C191 carriers (Plt;0.000 1), and the relative risk of CYP2C192,3 carriers increased 92% within one month (Plt;0.000 1); c) as for bleeding events, there were no significant differences between CYP2C192,3 carriers and CYP2C191 carriers. Conclusion Compared with CYP2C191 carriers, CYP2C192,3 carriers have a higher risk of stent thrombosis in clopidogrel-treated patients, but there are few differences in cardiovascular and bleeding events between the two carriers. Therefore, CYP2C192,3 carriers with cardiovascular diseases and ready to receive PCT are suggested to pay more attention to stent thrombosis when using clopidogrel. We propose that patients with cardiovascular diseases and ready to receive PCT should have CYP2C19 tests to determine the use of antiplatelet drug (clopidogrel) to avoid thrombus.
Objective To summarize results of the correlation of tumor necrosis factor-α (TNF-α) promoter –308A/G polymorphism with systemic lupus erythematosus (SLE) susceptibility in Chinese populations. Methods We collected all the publications about the correlation between TNF-α promoter –308A/G polymorphism and SLE in Chinese populations by searching PubMed, EBSCO, CBM, CNKI and Wanfang Data before the date of March 20, 2010. Meta-analysis was performed for checking the difference between two groups about genotypes such as AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele. Results A total of 8 studies involving 731 SLE patients and 901 healthy people were included. The meta-analysis of total populations showed that, there was no significant correlation between A allele and increased SLE risk (OR=1.42, 95%CI 0.97 to 2.09, P=0.07); the meta-analyses of populations in different regions showed there was no significant correlation of A allele and increased SLE risk in Chinese Taiwan populations (OR=1.04, 95%CI 0.77 to 1.40, P=0.82). Moreover, there was no significant difference between SLE group and control group in the genotypes of AA versus GG, GA versus GG, AA versus GG+GA, and GA+AA versus GG.Conclusion This meta-analysis dosen’t demonstrate the correlation between TNF-α promoter–308A/G polymorphism and SLE in Chinese populations.
ObjectiveTo evaluate the association between the Single Nucleotide Polymorphism (SNP) BsmI (rs1544410) in the vitamin D receptor gene and the susceptibility of coronary artery disease. MethodsDatabases including PubMed, Web of Science, CNKI, WanFang Data, VIP and CBM were searched from inception to May, 2016 to collect case-control studies about SNP BsmI (rs1544410) in the vitamin D receptor gene and the susceptibility of coronary artery disease. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then Meta-analysis was performed by using RevMan 5.3. ResultsA total of seven studies were included, which involved 2182 patients and 5925 controls. The results of meta-analyses showed that the B allele and BB genotype in rs1544410 was associated with the risk of coronary artery disease (B vs. b:OR=1.36, 95%CI 1.03 to 1.79, P=0.03; BB vs. bb:OR=1.70, 95%CI 1.06 to 2.72, P=0.03; BB+Bb vs. bb:OR=1.52, 95%CI 1.00 to 2.30, P=0.05). Subgroup analysis by age showed that rs1544410 was associated with the risk of coronary artery disease in the age <65(B vs. b:OR=1.65, 95%CI 1.00 to 2.73, P=0.05; BB vs. Bb+ bb:OR=1.79, 95%CI 1.08 to 2.97, P=0.02; BB vs. bb:OR=2.64, 95%CI 1.12 to 6.25, P=0.03). Subgroup analysis by ethnicity showed that rs1544410 was associated with the risk of coronary artery disease in Caucasians (B vs. b:OR=1.47, 95%CI 1.10 to 1.97, P=0.01; BB+Bb vs. bb:OR=1.71, 95%CI 1.09 to 2.68, P=0.02; BB vs. Bb+bb:OR=1.39, 95%CI 1.01 to 1.92, P=0.05; BB vs. bb:OR=1.80, 95%CI 1.10 to 2.95, P=0.03). Subgroup analysis by genotyping methods showed that rs1544410 was associated with the risk of coronary artery disease in the TaqMan (B vs. b:OR=2.18, 95%CI 1.06 to 4.45, P=0.03; BB+Bb vs. bb:OR=3.32, 95%CI 1.06 to 10.40, P=0.04; BB vs. bb:OR=3.31, 95%CI 1.06 to 10.30, P=0.04). Subgroup analysis by diagnostic criteria for cases showed that rs1544410 was associated with the risk of coronary artery disease in the ECG (B vs. b:OR=1.15, 95%CI 1.02 to 1.29, P=0.02; BB+Bb vs. bb:OR=1.22, 95%CI 1.02 to 1.45, P=0.03; BB vs. bb:OR=1.31, 95%CI 1.03 to1.67, P=0.03). ConclusionBsmI (rs1544410) B allele may have a significant association with the high risk of coronary artery disease especially the Caucasians and the ones with age <65.
Behcet's Disease (BD) is a multisystem vasculitis characterized by disease alternated with recurrent episodes and remissions, involving genital, oral, ocular uvea, cutaneous, and articular manifestations. The nuclear factor (NF)-κB signaling pathway paly an important role in the BD progression. It encompasses diverse gene, protein, and cellular regulatory mechanisms operating across various levels, alongside microbiological and experimental studies involving animals and cells. At the protein research findings, activation of the NF-κB pathway in BD patients is marked by elevated plasma levels of soluble CD40 ligand, which stimulates neutrophils to release reactive oxygen species and extracellular traps, thereby promoting inflammation. At the cellular research findings, macrophages in BD patients polarize towards classically activated macrophages phenotype through the NF-κB pathway, exacerbating the inflammatory response. The activation of NF-κB is associated with increased expression of anti-apoptotic proteins in T cells, leading to prolonged inflammation. Microbiological investigations reveal that the decreased gut microbiota diversity in BD patients compromises intestinal barrier integrity. NF-κB pathway involvement in regulating neutrophil and type 1 helper T cell (Th) 1/Th17 cell function worsens inflammation. Genetically, BD patients exhibit polymorphisms in immune regulatory genes, which contribute to inflammation through the NF-κB pathway. Mutations in NF-κB-associated genes elevate the risk of BD, while mutations in the endogenous inhibitor A20 lead to abnormal NF-κB activity, sustaining inflammation. Animal experiments and in vitro experiments corroborate the efficacy of NF-κB inhibitors in attenuating inflammation. Targeting upstream inflammatory factors within the NF-κB pathway yields positive outcomes in BD patients. In summary, the NF-κB signaling pathway plays a pivotal role in the development of BD. Developing NF-κB inhibitors may open new avenues for treating BD. Further research is necessary to comprehensively elucidate the precise mechanisms by which NF-κB operates in the pathogenesis of BD, as well as its potential clinical applications in therapy.