Objective To reveal the association between the single nucleotide polymorphism (SNP) of v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene rs17820943 locus and non-syndromic cleft l ip with or without cleft palate (NSCL/P) in the southern Chinese Han population. Methods Genotyping of MAFB gene rs17820943 polymorphism was carried out in 300 patients with NSCL/P, 354 normal controls, and an additional 168 case-parent trios with matrix-assisted laser desorption/ionisation time-of-fl ight (MALDI-TOF) mass spectrometry. Then based on the genotypingresults, both a case-control association study and a case-parent trio association study were performed. Results Significant differences were found in the allele and genotype frequencies of rs17820943 locus between case and control groups (Pallele=0.001 and Pgenotype=0.002, respectively). To be specific, the odds radio (OR) values and 95% confidence interval (95%CI) of allele T (frequencies of cases ∶ controls = 0.358 ∶ 0.448) and genotype TT (frequencies of cases ∶ controls = 0.110 ∶ 0.195) were ORT = 0.69 (95%CI: 0.55-0.86) and ORTT = 0.43 (95%CI: 0.26-0.70), respectively. Subsequent case-parent trio analysis also indicated an association between MAFB rs17820943 variant and the risk of NSCL/P (ORT vs. C = 0.55, 95%CI: 0.41-0.75, P value of transmission disequilibrium test was 0.000). Conclusion Polymorphism of MAFB gene rs17820943 locus is associated with NSCL/P in the southern Chinese Han population; MAFB rs17820943 variant may be a susceptible gene of NSCL/P.
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.
Objective To evaluate the relationship between angiotension-converting enzyme (ACE) gene polymorphism and susceptibility to cerebral hemorrhage among the Han Chinese population. Methods We electronically searched CNKI, CBM, VIP, and Wanfang technological periodical full-text databases from January, 1998 to January, 2009. We identified case-control studies of ACE gene polymorphism and cerebral hemorrhage among the Han Chinese population, and assessed the quality of included studies. The data were quantitatively analyzed by RevMan 4.3 software. Results Meta-analysis results showed that the pooled OR value of cerebral hemorrhage subjects among the Han Chinese population with at least one D allele was 1.42 (95%CI1.13 to1.78). The pooled OR values of cerebral hemorrhage with DD and II genotype were 1.9 (95%CI1.32 to 2.74) and 0.80 (95%CI0.63 to 1.01) respectively. Conclusion ACE gene polymorphism is significantly associated with susceptibility to cerebral hemorrhage in the Han Chinese `population.
ObjectiveTo systematically review the relationship between T309G polymorphism of murine double minute 2 (MDM2) gene and susceptibility of prostate cancer. MethodsThe PubMed, Embase, WanFang Data, CNKI databases were electronically searched to collect case-control studies related to the objectives from inception to May, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 14.0 software. ResultsA total of 10 studies involving 5 781 patients and 5 477 healthy controls were included. The results of meta-analysis showed that the MDM2 gene T309G polymorphism was not associated with preeclampsia (allele model G vs. T: OR=0.89, 95%CI 0.77 to 1.04, P=0.13; homozygote model GG vs. TT: OR=0.86, 95%CI 0.64 to 1.16, P=0.32; heterozygote model TG vs. TT: OR=1.04, 95%CI 0.86 to 1.26, P=0.12; dominant model GG+TG vs. TT: OR=0.96, 95%CI 0.89 to 1.04, P=0.36; recessive model GG vs. TG+TT: OR=0.84, 95%CI 0.63 to 1.14, P=0.27). The results of subgroup analysis based on ethnicity and source of control were similar to the overall results. Sensitivity analysis showed that the results were robust. Conclusion?Current evidence shows that the MDM2 gene T309G polymorphism is not associated with prostate cancer susceptibility. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To investigate association between –174C/G genetic polymorphism of interleukin-6 (IL-6) and susceptibility to gastric cancer by conducting a meta-analysis. Methods Such databases as PubMed, Embase, The Cochrane Library, Web of Science, CNKI, VIP, and Wanfang Data were searched from inception to January 2017 to collect case-control studies about the correlation between the –174C/G genetic polymorphism of IL-6 and susceptibility to gastric cancer. For the population genotype distributions of both the gastric cancer group and the control group, their odds ratios (OR) and 95% confidence intervals (CI) were taken as the effect indexes were applied to conduct meta-analysis in the homozygote model (CC vs. GG), heterozygote model (GC vs. GG), dominant model (CC+CG vs. GG), recessive model (CG+GG vs. CC), and allelic genetic model (C vs. G). Two reviewers independently screened the literatures, extracted the data, and evaluated the quality of the included studies. The meta-analysis was performed using Stata 12.0 software. Results Thirteen articles were included in the final meta-analysis, covering a total of 2 062 gastric cancer cases and 3 152 controls. The results of meta-analysis showed that there was no correlation between the IL-6 –174C/G genetic polymorphism and the risk of gastric cancer〔CC vs. GG: OR=1.33, 95% CI (0.92, 1.94); GC vs. GG: OR=1.32, 95% CI (0.96, 1.82); CC+CG vs. GG: OR=1.32, 95% CI (0.97, 1.80); CG+GG vs. CC: OR=0.89, 95% CI (0.67, 1.17); C vs. G: OR=1.22, 95% CI (0.98, 1.54)〕. But the results of the subgroup analysis showed there was a significant association between the IL-6 –174 C/G genetic polymorphism and the risk of gastric cancer in Asians〔CC vs. GG: OR=1.80, 95% CI (1.29, 2.50); GC vs. GG: OR=1.51, 95% CI (1.20, 1.90); CC+CG vs. GG: OR=1.60, 95% CI (1.30, 1.96); CG+GG vs. CC: OR=0.60, 95% CI (0.44, 0.83); C vs. G: OR=1.59, 95% CI (1.24, 2.03)〕. However, no association was found in Europeans〔CC vs. GG: OR=1.11, 95% CI (0.90, 1.39); GC vs. GG: OR=1.16, 95% CI (0.98, 1.37); CC+CG vs. GG: OR=1.12, 95% CI (0.96, 1.32); CG+GG vs. CC: OR=1.07, 95% CI (0.88, 1.30); C vs. G: OR=1.04, 95% CI (0.78, 1.41)〕 . Conclusion IL-6 –174C/G genetic polymorphism is associated with susceptibility to gastric cancer in Asians, which is not associated with susceptibility to gastric cancer in Europeans.
Objective To perform a meta-analysis and investigate the correlation between angiotensin-I converting enzyme gene insertion (I), deletion (D) polymorphism and type 2 diabetic nephropathy, assessing the bias of small sample size study and heterogeneity between studies. Methods MEDLINE, EBSCO, EMbase, PubMed, CHKD, CNKI, CBM, VIP and WanFang Data were searched (from January 1994 to March 18th 2011) for relevant case-control studies. Two reviewers independently identified the literature according to inclusion and exclusion criteria. Also references of the included literature were retrieved. Then data were extracted and assessed by the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.0.0 software. Results A total of 61 studies comprising 9 979 cases and 7 252 control subjects were included. There was b evidence of heterogeneity (Plt;0.05, I2=60%) and a random effect model was employed to summarize the data. Results of meta-analysis showed that T2DM patients with II genotype had lower incidences of DN than those with DD+DI genotype (OR=0.65, 95%CI 0.57 to 0.74). The results of subgroup meta-analysis showed that Chinese, Japanese and Brazilians patients with II genotype had lower incidences of DN. However, there were no relation among Caucasus, Middle-East, Indian, Mexican, Korean, and Malaysian patients. Conclusion As for T2DM patients, their angiotensin-I converting enzyme gene insertion (I), deletion (D) polymorphism relates to DN. T2DM patients with II genotype have lower incidences of DN. But the difference of this relation varies with ethnicity.
Objective To investigate the mutations of quinolone resistance determinational region ( QRDR) in fluoroquinolon-resistant Pseudomonas aeruginosa strains isolated from patients with nosocomial pneumonia. Methods Eight-four Pseudomonas aeruginosa strains isolated from patients with nosocomial pneumonia in Xinhua Hospital during January 2006 to December 2007, from whom fluoroquinolon-resistant resisitant ( case) and fluoroquinolon-susceptible ( control ) Pseudomona aeruginosa were identified. The mutation of QRDR was tested by restriction fragment length polymorphism ( RFLP) and gene sequencing.The relationship between QRDR mutations and clinical prescription was analyzed. Results Mutation in QRDR was found in 42 isolates among the 50 fluoroquinlon-resisitant isolates( 84. 0% ) , while no mutation was found in fluoroquinlon-susceptible isolates. The mutation in GyrB Ser464 was found in 34 isolates ( 68. 0% ) . There was statistical difference in the usage of β-lactams between the GyrB-Ser464-mutated group and the non-GyrB-Ser464-mutated group( OR = 11. 3, P = 0. 003 and OR = 3. 5, P = 0. 023) , also in the time of fluoroquinolon usage before isolated ( P = 0. 038) . Conclusions The mutation of QRDR is contributing to fluoroquindor-resisitance of Pseudomona aeruginosa, most of which lies in GyrB Ser464.Abuse of β-lactams and fluoroquinolon may be the risk factors of mutation in GyrB Ser464.
摘要:目的:研究高血壓病患者脂蛋白脂肪酶(liportein lipase, LPL)S447X基因多態性與認知功能之間的關系。方法: 對2008年1月至2008年11月在四川大學華西醫院醫院門診就診的原發性高血壓患者190例,收集一般資料,采用國際通用的簡易智力狀況量表測驗認知功能,計算認知評分,用聚合酶鏈反應限制性片段長度多態性(PCRRFLP)技術測定LPL S447X基因多態性。同時測定膽固醇、甘油三酯、空腹血糖、空腹胰島素及餐后2h血糖、餐后2h胰島素水平。結果: 高血壓病患者認知功能正常組和認知功能障礙組組間LPLS447X基因的基因型和基因頻率差異均無統計學意義(Pgt;0.05), SS和SX頻率分別為92.6%、7.4%,S和X等位基因頻率分別為96.3%和3.7%。結論: LPLS447X 基因多態性可能與高血壓認知功能障礙無明顯相關性。Abstract: Objective:To study the relationship between liportein lipase(LPL) S447X polymorphism and cognitive function in patients with primary hypertension. Methods:One hundred and ninety hypertensive patients from January 2008 to November 2008 in West China Hospital of Si Chuan University. We collected the general data and applied the Mini Mental State Examination to test the cognitive function and computed score. PCRRELP method was used to analyze the LPL S447X gene polymorphism. Total cholesterol、triglyeride、fasting plasma glucose and postprandial blood sugar、fasting insulin and postprandial plasma insulin were collected. Results:In primary hypertensive patients, both of the genotype frequency and the allele frequency of the LPL S447X polymorphism were not different between the cognitive normal group and the cognitive impaired group (Pgt;0.05). SS genotype was present in 0926 of the population, SX genotype was present in 0.074 of the population. allele frequencies were 0.963 for S allele and 0.037 for X allele. Conclusion:This results suggest S447X polymorphism in LPL with primary hypertension may not be associated with cognitive impairment. And age and postprandial plasma insulin level are the risk factors of hypertensive cognitive impairment.
ObjectivesTo investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement, to forecast the anticoagulation therapy with warfarin reasonable dosage, and to realize individualized management of anticoagulation monitoring. MethodsWe selected 103 patients between January 1, 2011 and December 31, 2012 in West China Hospital of Sichuan University who were treated by oral warfarin after heart valve replacement with monitoring anticoagulation by international normalized ratio (INR) in Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. There were 32 males and 71 female at age of 21-85 (48.64± 11.66) years. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method and gene sequencing technology. Warfarin concentration in plasma was determined by high performance liquid chromatography (HPLC) method. The activity of coagulation factorⅡ, Ⅶ, Ⅸ, Ⅹwas determined by Sysmex CA7000 analyzer. ResultsThe multivariate linear regression analysis showed that age, body surface area, and coagulation factor activity had no significant effect on warfarin dosage. While the gene polymor-phisms of CYP2C9 and VKORC1, warfarin concentration, and age had significant contributions to the overall variability in warfarin dose with decisive coefficients at 1.2%, 26.5%, 43.4%, and 5.0% respectively. The final equation was:Y=1.963-0.986× (CYP2C9* 3) +0.893× (VKORC1-1639) +0.002× (warfarin concentration)-0.019× (age). ConclusionMultiple regression equation including gene polymorphisms of CYP2C9 and VKORC1, non-genetic factors of coagulation factor activity, warfarin concentration, age, and body surface area can predict reasonable dosage of warfarin for anticoagulation to achieve individualized management of anticoagulation monitoring and reduce the anticoagulation complications.
Objective To systematically review the correlation between epidermal growth factor (EGF) 61A/G polymorphism and the risk of esophageal carcinoma. Methods Such databases as PubMed, EMbase, CJFD, CBM, CNKI, VIP and WanFang Data were electronically searched from inception to January 1st, 2013, to collect case-control studies on the correlation between epidermal growth factor (EGF) 61A/G polymorphism and the risk of esophageal carcinoma. Two reviewers independently identified the literature according to inclusion and exclusion criteria, extracted data, and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 and Stata 12.0 software. Results A total of six studies involving 1 448 cases and 1 728 control subjects were included. The results of meta-analysis showed that, there was no significant association between EGF 61A/G polymorphism and the risk of esophageal carcinoma (dominant model: AG+GG vs. AA: OR=1.22, 95%CI 0.91 to 1.65; and recessive model: GG vs. AG+AA: OR=1.35, 95%CI 0.94 to 1.94; AG vs. AA: OR=1.12, 95%CI 0.93 to 1.35; GG vs. AA: OR=1.43, 95%CI 0.83 to 2.47). The results of subgroup analysis grouped by ethnicity showed that, EGF 61A/G polymorphism increased the risk of esophageal carcinoma of the White population (dominant model: AG+GG vs. AA: OR=1.39, 95%CI 1.14 to 1.71; and recessive model: GG vs. AG+AA: OR=1.75, 95%CI 1.37 to 2.25; GG vs. AA: OR=1.93, 95%CI 1.47 to 2.55). However, it had no correlation to the risk of esophageal carcinoma of Asian population. Conclusion Current studies showed that, EGF 61A/G polymorphism is not associated with susceptibility to esophageal carcinoma , but it may increase the risk of esophageal carcinoma in White population. Due to limited quality and quantity of the included studies, the above conclusion needs to be verified by more studies with large sample size.