Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patie...Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α (-238 and -308) and IL-1RA (+2018) was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) and SYBR green-based quantitative polymerase chain reaction {qPCR), respectively. Unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidential intervals (Cl) for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index (BMI), and status of smoking and alcohol consumption except for age (P=O.O01) and blood type (P=0.042). The frequencies of TNF-c((-238) and IL-1RA (+2018) genotypes in cases were significantly different from those in controls, (P=O.O01 and P=0.O02, respectively), while a borderline significant difference was found in the frequencies of TNF-α(-308) between cases and controls (P=0.063). The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα(-308), TNF-α(-238) and IL-1RA (+2018) were 2.8 (95% Ch 2.1-7.5), 20.9 (95% Ch 2.8-236.4) and 4.0 (95% CI: 2.6-10.2), respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct (-238, -308) and IL-1RA (+2018) are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.展开更多
BACKGROUND Type 1 diabetes(T1D)is a severe and prevalent metabolic disease.Due to its high heredity,an increasing number of genome-wide association studies have been performed,most of which were from hospital-based ca...BACKGROUND Type 1 diabetes(T1D)is a severe and prevalent metabolic disease.Due to its high heredity,an increasing number of genome-wide association studies have been performed,most of which were from hospital-based case-control studies with a relatively small sample size.The association of single nucleotide polymorphisms(SNPs)and T1D has been less studied and is less understood in natural cohorts.AIM To investigate the significant variants of T1D,which could be potential biomarkers for T1D prediction or even therapy.METHODS A genome-wide association study(GWAS)of adult T1D was performed in a nested case-control study(785 cases vs 804 controls)from a larger 5-year cohort study in Suzhou,China.Potential harmful or protective SNPs were evaluated for T1D.Subsequent expression and splicing quantitative trait loci(eQTL and sQTL)analyses were carried out to identify target genes modulated by these SNPs.RESULTS A harmful SNP for T1D,rs3117017[odds ratio(OR)=3.202,95%confidence interval(CI):2.296-4.466,P=9.33×10-4]and three protective SNPs rs55846421(0.113,0.081-0.156,1.76×10-9),rs75836320(0.283,0.205-0.392,1.07×10-4),rs362071(0.568,0.495-0.651,1.66×10-4)were identified.Twenty-two genes were further identified as potential candidates for T1D onset.CONCLUSION We identified a potential genetic basis of T1D,both protective and harmful,using a GWAS in a larger nested case-control study of a Chinese population.展开更多
Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene ...Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls (P 〈 0.01 and P = 0.02). Furthermore, compared with the GG + GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.16–2.79, P 〈 0.01). Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke (OR = 1.94,95% CI : 1.13–3.33, P = 0.02). The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis (OR = 1.49, 95% CI: 1.10–2.00, P 〈 0.01). These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559).展开更多
BACKGROUND The expression of macrophage inhibitory factor-1(MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with r...BACKGROUND The expression of macrophage inhibitory factor-1(MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus(HCV) infection.METHODS This case-control study enrolled 178 patients with chronic hepatitis C(CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group(P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase(AST), type III procollagen N-terminal peptide(known as PIIINP), type IV collagen, and HCV RNA(P < 0.05), whereas negatively correlated with total protein and albumin(P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups(P < 0.05). The allele frequency maintained significant difference after Bonferroni correction(Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC(P < 0.05). Linkage disequilibrium(LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups(P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes(P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype(P = 0.009, after Bonferroni correction).CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.展开更多
OBJECTIVE: Previous reports have demonstrated that X-ray repair cross-complementing gene 1 (XRCCl) Arg399GIn polymorphism is a possible risk factor for several cancers. Published data on the association of XRCCl Ar...OBJECTIVE: Previous reports have demonstrated that X-ray repair cross-complementing gene 1 (XRCCl) Arg399GIn polymorphism is a possible risk factor for several cancers. Published data on the association of XRCCl Arg399GIn polymorphism with glioma susceptibility have generated conflicting results. This study is designed to precisely estimate the relationship. DATA RETRIEVAL: A computer-based online retrieval of Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure was performed to search papers regarding association of XRCC1 Arg399GIn polymorphisms with glioma published up to April 2012. SELECTION CRITERIA: Two investigators selected data independently. Meta analysis was then performed for the selected studies using STATA 11.0 software after strict selection. Heterogeneity test, sensitivity analysis and publication bias assessments were then conducted. MAIN OUTCOME MEASURES: Association of XRCCl Arg399GIn polymorphism with glioma risk. RESULTS: A total of nine case-controlled studies comprising 2 326 cases and 3 610 controls were selected for final analysis. The overall data failed to indicate a significant association of XRCCl Arg399GIn polymorphism with glioma risk (Gin/Gin vs. Arg/Arg: odds ratio (OR) = 1.11; 95% confidence interval (Cl) = 0.94-1.31; dominant model: OR = 1.06; 95%C/= 0.95-1.18; recessive model: OR = 1.04; 95%C/= 0.81-1.34). However, subgroup analysis regarding ethnicity showed an increased risk among Asians (Gin/Gin vs. Arg/Arg OR = 1.40; 95%C/= 1.10-1.78; recessive model: Caucasians or mixed ethnicities. OR = 1.70; 95%Cl = 1.17-2.46; dominant mode OR = 1.46; 95%C/= 1.04-2.05) but not CONCLUSION: XRCCl Arg399GIn polymorphism might modify the susceptibility to glioma among Asians but not Caucasians. Further large and well-designed studies are needed to confirm this conclusion.展开更多
Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Scie...Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Science were searched for case-control studies on the association between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.The retrieval period was from the establishment of the database to November 2020.Two researchers independently screened the literature,extracted the data,evaluated the risk of bias in the included studies,and used Stata 14.0 software for meta-analysis.Results A total of 48 case-control studies were included,with 10520 and 44049 cases in the case and control groups,respectively.The meta-analysis results showed that rs4132061 and rs11978267 of IKZF1 were significantly correlated with the risk of acute lymphoblastic leukemia(ALL).Conclusion Current evidence indicates that rs4132061 and rs11978267 of IKZF1 are significantly associated with the risk of B-cell ALL.展开更多
Background:Chronic obstructive pulmonary disease(COPD)is a leading cause of morbidity and mortality worldwide.Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the P...Background:Chronic obstructive pulmonary disease(COPD)is a leading cause of morbidity and mortality worldwide.Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1,a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function.The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.Methods:We performed a case-control study including 296 patients with COPD and 300 healthy individuals.Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants.Odds ratios(ORs)and 95%confidence intervals(95%CIs)were estimated using logistic regression analysis after adjustment for age,gender,and smoking.Results:In total,28 single-nucleotide polymorphisms were identified in patients with COPD.Among them,"A"allele of rs28491365(OR:1.388,95%CI:1.055-1.827,P=0.018),and"G"alleles of rs10512248(OR:1.299,95%CI:1.021-1.653,P=0.033)and rs28705285(OR:1.359,95%CI:1.024-1.803,P=0.033;respectively)were significantly associated with an increased COPD risk.Genetic model analysis revealed that the"T/T"genotype of rs34695652 was associated with a decreased COPD risk under the recessive model(OR:0.490,95%CI:0.270-0.880,P=0.010),whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age,gender,and smoking status(OR:6.364,95%CI:1.220-33.292,P=0.028).Conclusions:The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA ris...BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.展开更多
文摘Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α (-238 and -308) and IL-1RA (+2018) was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) and SYBR green-based quantitative polymerase chain reaction {qPCR), respectively. Unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidential intervals (Cl) for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index (BMI), and status of smoking and alcohol consumption except for age (P=O.O01) and blood type (P=0.042). The frequencies of TNF-c((-238) and IL-1RA (+2018) genotypes in cases were significantly different from those in controls, (P=O.O01 and P=0.O02, respectively), while a borderline significant difference was found in the frequencies of TNF-α(-308) between cases and controls (P=0.063). The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα(-308), TNF-α(-238) and IL-1RA (+2018) were 2.8 (95% Ch 2.1-7.5), 20.9 (95% Ch 2.8-236.4) and 4.0 (95% CI: 2.6-10.2), respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct (-238, -308) and IL-1RA (+2018) are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.
基金the National Science Foundation for Young Scientists of China(No.81602919)the National Science Foundation for Young Scientists of China(No.82070814)+1 种基金the Suzhou Science and Technology Development Plan(No.SYS2018099)and the 5th Suzhou Health Talent Program(No.GSWS2019071).
文摘BACKGROUND Type 1 diabetes(T1D)is a severe and prevalent metabolic disease.Due to its high heredity,an increasing number of genome-wide association studies have been performed,most of which were from hospital-based case-control studies with a relatively small sample size.The association of single nucleotide polymorphisms(SNPs)and T1D has been less studied and is less understood in natural cohorts.AIM To investigate the significant variants of T1D,which could be potential biomarkers for T1D prediction or even therapy.METHODS A genome-wide association study(GWAS)of adult T1D was performed in a nested case-control study(785 cases vs 804 controls)from a larger 5-year cohort study in Suzhou,China.Potential harmful or protective SNPs were evaluated for T1D.Subsequent expression and splicing quantitative trait loci(eQTL and sQTL)analyses were carried out to identify target genes modulated by these SNPs.RESULTS A harmful SNP for T1D,rs3117017[odds ratio(OR)=3.202,95%confidence interval(CI):2.296-4.466,P=9.33×10-4]and three protective SNPs rs55846421(0.113,0.081-0.156,1.76×10-9),rs75836320(0.283,0.205-0.392,1.07×10-4),rs362071(0.568,0.495-0.651,1.66×10-4)were identified.Twenty-two genes were further identified as potential candidates for T1D onset.CONCLUSION We identified a potential genetic basis of T1D,both protective and harmful,using a GWAS in a larger nested case-control study of a Chinese population.
基金supported by a grant from the National Natural Science Foundation of China,No.81070913
文摘Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls (P 〈 0.01 and P = 0.02). Furthermore, compared with the GG + GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.16–2.79, P 〈 0.01). Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke (OR = 1.94,95% CI : 1.13–3.33, P = 0.02). The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis (OR = 1.49, 95% CI: 1.10–2.00, P 〈 0.01). These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559).
基金Supported by the Medical and Health Research Science and Technology Plan Project of Zhejiang Province,No. 2016KYB191。
文摘BACKGROUND The expression of macrophage inhibitory factor-1(MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus(HCV) infection.METHODS This case-control study enrolled 178 patients with chronic hepatitis C(CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group(P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase(AST), type III procollagen N-terminal peptide(known as PIIINP), type IV collagen, and HCV RNA(P < 0.05), whereas negatively correlated with total protein and albumin(P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups(P < 0.05). The allele frequency maintained significant difference after Bonferroni correction(Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC(P < 0.05). Linkage disequilibrium(LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups(P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes(P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype(P = 0.009, after Bonferroni correction).CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.
文摘OBJECTIVE: Previous reports have demonstrated that X-ray repair cross-complementing gene 1 (XRCCl) Arg399GIn polymorphism is a possible risk factor for several cancers. Published data on the association of XRCCl Arg399GIn polymorphism with glioma susceptibility have generated conflicting results. This study is designed to precisely estimate the relationship. DATA RETRIEVAL: A computer-based online retrieval of Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure was performed to search papers regarding association of XRCC1 Arg399GIn polymorphisms with glioma published up to April 2012. SELECTION CRITERIA: Two investigators selected data independently. Meta analysis was then performed for the selected studies using STATA 11.0 software after strict selection. Heterogeneity test, sensitivity analysis and publication bias assessments were then conducted. MAIN OUTCOME MEASURES: Association of XRCCl Arg399GIn polymorphism with glioma risk. RESULTS: A total of nine case-controlled studies comprising 2 326 cases and 3 610 controls were selected for final analysis. The overall data failed to indicate a significant association of XRCCl Arg399GIn polymorphism with glioma risk (Gin/Gin vs. Arg/Arg: odds ratio (OR) = 1.11; 95% confidence interval (Cl) = 0.94-1.31; dominant model: OR = 1.06; 95%C/= 0.95-1.18; recessive model: OR = 1.04; 95%C/= 0.81-1.34). However, subgroup analysis regarding ethnicity showed an increased risk among Asians (Gin/Gin vs. Arg/Arg OR = 1.40; 95%C/= 1.10-1.78; recessive model: Caucasians or mixed ethnicities. OR = 1.70; 95%Cl = 1.17-2.46; dominant mode OR = 1.46; 95%C/= 1.04-2.05) but not CONCLUSION: XRCCl Arg399GIn polymorphism might modify the susceptibility to glioma among Asians but not Caucasians. Further large and well-designed studies are needed to confirm this conclusion.
基金Supported by the National Key Project of Neonatal Children (No. 1311200003303)Grants from the Science and Technology Bureau of Sichuan Province (No. 2021YJ0211 to Jinlin Wu)Grants from the Health Planning Committee of Sichuan Province (No. 20PJ070 to Jinlin Wu)
文摘Objective The aim of the study was to systematically evaluate the correlation between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.Methods Computer databases including PubMed,EMBASE,and Web of Science were searched for case-control studies on the association between IKZF1 polymorphisms and the risk of acute lymphoblastic leukemia.The retrieval period was from the establishment of the database to November 2020.Two researchers independently screened the literature,extracted the data,evaluated the risk of bias in the included studies,and used Stata 14.0 software for meta-analysis.Results A total of 48 case-control studies were included,with 10520 and 44049 cases in the case and control groups,respectively.The meta-analysis results showed that rs4132061 and rs11978267 of IKZF1 were significantly correlated with the risk of acute lymphoblastic leukemia(ALL).Conclusion Current evidence indicates that rs4132061 and rs11978267 of IKZF1 are significantly associated with the risk of B-cell ALL.
基金Central South University Clinical Data System for Pulmonary Inflammatory Diseases.
文摘Background:Chronic obstructive pulmonary disease(COPD)is a leading cause of morbidity and mortality worldwide.Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1,a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function.The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.Methods:We performed a case-control study including 296 patients with COPD and 300 healthy individuals.Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants.Odds ratios(ORs)and 95%confidence intervals(95%CIs)were estimated using logistic regression analysis after adjustment for age,gender,and smoking.Results:In total,28 single-nucleotide polymorphisms were identified in patients with COPD.Among them,"A"allele of rs28491365(OR:1.388,95%CI:1.055-1.827,P=0.018),and"G"alleles of rs10512248(OR:1.299,95%CI:1.021-1.653,P=0.033)and rs28705285(OR:1.359,95%CI:1.024-1.803,P=0.033;respectively)were significantly associated with an increased COPD risk.Genetic model analysis revealed that the"T/T"genotype of rs34695652 was associated with a decreased COPD risk under the recessive model(OR:0.490,95%CI:0.270-0.880,P=0.010),whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age,gender,and smoking status(OR:6.364,95%CI:1.220-33.292,P=0.028).Conclusions:The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.
基金Supported by Japan Society for the Promotion of Science,No.21406011.
文摘BACKGROUND Cholangiocarcinoma(CCA)is an intractable cancer,and its incidence in north eastern Thailand is the highest worldwide.Infection with the liver fluke Opisthorchis viverrini(OV)has been associated with CCA risk.However,animal experiments have suggested that OV alone does not induce CCA,but its combination with a chemical carcinogen like nitrosamine can cause experimentally induced CCA in hamsters.Therefore,in humans,other environmental and genetic factors may also be involved.AIM To examine relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes.METHODS This hospital-based case-control study enrolled 95 case-control pairs matched by age(±5 years)and sex.We examined relations between risk for CCA and genetic polymorphisms in carcinogenmetabolizing and inflammation-related genes,serum anti-OV,alcohol consumption,and smoking.Polymorphisms of CYP2E1,IL-6(-174 and-634),IL-10(-819),and NF-κB(-94)and their cooccurrence with polymorphisms in the drug-metabolizing enzyme gene GSTT1 or GSTM1 were also analyzed.RESULTS Although CCA risk was not significantly associated with any single polymorphism,persons with the GSTT1 wild-type and CYP2E1 c1/c2+c2/c2 genotype had an increased risk(OR=3.33,95%CI:1.23-9.00)as compared with persons having the GSTT1 wild-type and CYP2E1 c1/c1 wild genotype.The presence of anti-OV in serum was associated with a 7-to 11-fold increased risk,and smoking level was related to an OR of 1.5-1.8 in multivariable analyses adjusted for each of the seven genetic polymorphisms.CONCLUSION In addition to infection with OV,gene-gene interactions may be considered as one of the risk factors for CCA development.