AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A ca...AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.展开更多
AIM" TO evaluate the impact of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 he...AIM" TO evaluate the impact of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer (PCR-CTPP) method. Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence interval (95% CI). RESULTS; Both ADH2*1 allele and ALDH2*1/*2 allele showed an increased risk of developing esophageal cancer. The adjusted OR (95% CI) for ADH2*1 allele compared with ADH2*2/*2 was 1.65 (95% CI = 1.02-2.68) and 1.67 (95% CI = 1.02-2.72) for ALDH2*1/*2 compared with ALDH2*1/*1. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83 (95% CI = 1.13-2.95). Furthermore, when compared with ADH2*2/*2 and ALDH2*1/*1 carriers, ADH2*1 and ALDH2*2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers展开更多
Objective:To explore genetic variations of Hypoderaeum conoideum collected from domestic ducks from 12 different localities in Thailand and Lao PDR,as well as their phylogenetic relationship with American and European...Objective:To explore genetic variations of Hypoderaeum conoideum collected from domestic ducks from 12 different localities in Thailand and Lao PDR,as well as their phylogenetic relationship with American and European isolates.Methods:The nucleotide sequences of their nuclear ribosomal DNA(ITS),mitochondrial cytochrome c oxidase subunit 1(CO1),and NADH dehydrogenase subunit 1(ND1)were used to analyze genetic diversity indices.Results:We found relatively high levels of nucleotide polymorphism in ND1(4.02%),whereas moderate and low levels were observed in CO1(2.11%)and ITS(0.96%),respectively.Based on these polymorphisms,the 20 ND1,12 CO1,and 18 ITS haplotypes were classified,and several common haplotypes were observed in all samples.At least three major lineages,namely American,European and Asian lineages,have been classified by phylogenetic analyses based on ND1 sequences.Conclusions:Our report demonstrates that the ND1 gene is the most suitable genetic marker to explore genetic variation and phylogenetic relationship of Hypoderaeum conoideum.However,a combination of all loci for ND1,CO1 and ITS would be of great value toward further genetic investigation of this endemic worldwide parasite.Thus,comprehensive molecular genetic analyses of Hypoderaeum conoideum from its worldwide distribution is needed to further understanding of the evolutionary and systematic relationships of this parasite.展开更多
Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to cla...Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to clarify the mechanism of CRC development related to alcohol consumption and to the presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179 controls) in patients with adenomas and intramucosal tumors who underwent endoscopic removal of all tumors. The amount of alcohol consumption was determined using a self-recorded questionnaire, and the tumor information was obtained from colonoscopy results. Blood samples were taken to analyze the following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The polymorphisms in ADH1B and ALDH2 had little influence on the development of colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu) group, an increased risk (OR = 3.4;95% CI 1.4 - 8.4;P = 0.009) was observed among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and Lys/Lys) group, an increased risk (OR = 4.2;95% CI 1.1 - 16.7;P = 0.041) was found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg). Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.展开更多
Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis...Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis C virus infection—being major contributors.Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13(HSD17B13)gene as a protective factor against the development and progression of these conditions.In this review,we summarized the current evidence surrounding the HSD17B13 rs72613567 variant,aiming to elucidate its impact on CLD risk and outcomes,and to explore the potential mechanisms behind its hepatoprotective effects.The rs72613567:TA variant induces a splice donor site mutation,resulting in a truncated,nonfunctional HSD17B13 protein.Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma(HCC)in patients with MASH,alcoholic liver disease,and hepatitis C virus infection.Moreover,the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients.Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC.Furthermore,inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH.However,the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated.Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.展开更多
目的:探讨MTHFR基因C677T多态性与非综合征型唇腭裂(nonsyndromic cleft lip with or without cleft pa-late,NSCL/P)相关性。方法:收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行MTHFR基因C677T位...目的:探讨MTHFR基因C677T多态性与非综合征型唇腭裂(nonsyndromic cleft lip with or without cleft pa-late,NSCL/P)相关性。方法:收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行MTHFR基因C677T位点多态性检测;用人群关联研究、传递不平衡检验(transmission-disequlibrium test,TDT)、单倍型相对风险率(haplotype-based haplotype relative risk,HHRR)、家系为基础的关联检验(family-basedas-sociation test,FBAT)等进行统计分析。结果:人群关联研究分析表明,子代、父亲、母亲的病例组和对照组之间基因型和等位基因的分布差异无统计学意义(P>0.05);子代、父亲、母亲组,CT基因型携带者相对于CC基因型携带者的OR分别为1.02(95%CI0.47~2.21)、0.62(95%CI0.29~1.32)、0.66(95%CI0.31~1.40);TT基因型携带者相对于CC基因型携带者的OR分别为1.10(95%CI0.44~2.74)、0.95(95%CI0.39~2.32)、0.68(95%CI0.28~1.66);T相对于C基因的OR分别为1.07(95%CI0.72~1.58)、0.98(95%CI0.66~1.46)、0.83(95%CI0.56~1.24)。携带有突变基因T并不能增加患NSCL/P的危险。病例组核心家庭分析表明,TDT检验χ2=1.817,P>0.05;HHRR检验χ2=1.76,P>0.05;FBAT检验Z=1.348,P>0.05。结论:没有发现MTHFRC677T多态性和NSCLP无关联性,该基因位点的变异可能不会导致中国东北地区人群NSCLP的发生。展开更多
研究了西方蜜蜂Apismellifera 6亚种———浙农大 1号意蜂 (ZND A .m .ligustica)、东北黑蜂 (A .m .ssp .)、卡尼鄂拉蜂 (A .m .carnica)、喀尔巴阡蜂 (A .m .carpatica)、高加索蜂 (A .m .caucasica)和乌克兰蜂 (A .m .acervorum)苹...研究了西方蜜蜂Apismellifera 6亚种———浙农大 1号意蜂 (ZND A .m .ligustica)、东北黑蜂 (A .m .ssp .)、卡尼鄂拉蜂 (A .m .carnica)、喀尔巴阡蜂 (A .m .carpatica)、高加索蜂 (A .m .caucasica)和乌克兰蜂 (A .m .acervorum)苹果酸脱氢酶Ⅱ的基因型频率、基因频率和杂合纯合度。浙农大 1号意蜂、喀尔巴阡蜂和高加索蜂的纯合度较高 ,但浙农大 1号意蜂等位基因c频率最高 ,喀尔巴阡蜂等位基因b频率最高 ,高加索蜂等位基因a频率最高 ;东北黑蜂、卡尼鄂拉蜂和乌克兰蜂是高度杂合的亚种 ,但东北黑蜂等位基因a、b、c的频率差异较小 ,卡尼鄂拉蜂和乌克兰蜂主要存在a、c两个等位基因 ,b出现频率很小 ;6亚种的基因型频率、基因频率和杂合纯合度都有极显著差异。这些差异将从遗传和生化角度为西方蜜蜂 6个亚种的鉴别提供依据。展开更多
文摘AIM:To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2 and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high risk area of Gansu Province, in Chinese males. METHODS: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYP2E1 *c1/*c2, ALDH2 *1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal cancer cases and 480 controls were recruited. RESULTS: Compared with controls, cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%) and a higher proportion of alcohol drinkers with > 30 drink-years (28.8% vs 13.5%). Heavier alcohol consumption and alcohol drinking with > 30 drink- years increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96-3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies were higher among patients with squamous cell carcinomas, at a level close to statistical significance (P = 0.014; P = 0.094; P = 0.0001 respectively). There were synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1 genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive ALDH2 encoded by ALDH2 *1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1 encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2 + *2/*2) and CYP2E1 (*c1/*c2 + *c2/*c2) genotypes, with a statistically significant difference; ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31) respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2 (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1 (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with ALDH2 (*1/*1) + ADH1B (*1/*2 + *2/*2), ALDH2 (*1/*1) + CYP2E1 (*c1/*c2 + *c2/*c2) respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76) respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no synergistic interaction. CONCLUSION: In our study, we found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for ESCC, and that there was a synergistic interaction among polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in Chinese males living in Gansu Province, China.
基金Supported partly by Sichuan University Youth Scientific Research Fund (2003) and partly by research fund from Sasakawa Classmate Association (065)
文摘AIM" TO evaluate the impact of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms on esophageal cancer risk. METHODS;One hundred and ninety-one esophageal cancer patients and 198 healthy controls from Yanting County were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase-chain-reaction with the confronting-two-pair-primer (PCR-CTPP) method. Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence interval (95% CI). RESULTS; Both ADH2*1 allele and ALDH2*1/*2 allele showed an increased risk of developing esophageal cancer. The adjusted OR (95% CI) for ADH2*1 allele compared with ADH2*2/*2 was 1.65 (95% CI = 1.02-2.68) and 1.67 (95% CI = 1.02-2.72) for ALDH2*1/*2 compared with ALDH2*1/*1. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk, the OR was 1.83 (95% CI = 1.13-2.95). Furthermore, when compared with ADH2*2/*2 and ALDH2*1/*1 carriers, ADH2*1 and ALDH2*2 carriers showed an elevated risk of developing esophageal cancer among non-alcohol drinkers
基金supported by Faculty of Medicine,Thammasat University,Thailand to CT,grant number 2-18/2562
文摘Objective:To explore genetic variations of Hypoderaeum conoideum collected from domestic ducks from 12 different localities in Thailand and Lao PDR,as well as their phylogenetic relationship with American and European isolates.Methods:The nucleotide sequences of their nuclear ribosomal DNA(ITS),mitochondrial cytochrome c oxidase subunit 1(CO1),and NADH dehydrogenase subunit 1(ND1)were used to analyze genetic diversity indices.Results:We found relatively high levels of nucleotide polymorphism in ND1(4.02%),whereas moderate and low levels were observed in CO1(2.11%)and ITS(0.96%),respectively.Based on these polymorphisms,the 20 ND1,12 CO1,and 18 ITS haplotypes were classified,and several common haplotypes were observed in all samples.At least three major lineages,namely American,European and Asian lineages,have been classified by phylogenetic analyses based on ND1 sequences.Conclusions:Our report demonstrates that the ND1 gene is the most suitable genetic marker to explore genetic variation and phylogenetic relationship of Hypoderaeum conoideum.However,a combination of all loci for ND1,CO1 and ITS would be of great value toward further genetic investigation of this endemic worldwide parasite.Thus,comprehensive molecular genetic analyses of Hypoderaeum conoideum from its worldwide distribution is needed to further understanding of the evolutionary and systematic relationships of this parasite.
文摘Background: Unlike with esophageal cancer, acetaldehyde levels and genetic polymorphisms in alcohol dehydrogenase have not yet been shown to be contributing factors for colorectal cancer (CRC). This study aimed to clarify the mechanism of CRC development related to alcohol consumption and to the presence of genetic polymorphisms in the alcohol dehydrogenase, ADH1B and aldehyde dehydrogenase, ALDH2. Methods: This was a case-control study (221 cases and 179 controls) in patients with adenomas and intramucosal tumors who underwent endoscopic removal of all tumors. The amount of alcohol consumption was determined using a self-recorded questionnaire, and the tumor information was obtained from colonoscopy results. Blood samples were taken to analyze the following polymorphisms: ALDH2 Glu504Lys and ADH1B His48Arg. Results: The polymorphisms in ADH1B and ALDH2 had little influence on the development of colorectal adenoma or intramucosal cancer. Patients with ALDH2 (Glu/Glu) were more tolerant of alcohol than those with ALDH2 (Glu/Lys and Lys/Lys). Next, we examined certain combinations of the ADH1B genotypes. In the ALDH2 (Glu/Glu) group, an increased risk (OR = 3.4;95% CI 1.4 - 8.4;P = 0.009) was observed among moderate/heavy drinkers with ADH1B (His/His). In the ALDH2 (Glu/Lys and Lys/Lys) group, an increased risk (OR = 4.2;95% CI 1.1 - 16.7;P = 0.041) was found among moderate/heavy drinkers with ADH1B (Arg/His and Arg/Arg). Conclusions: ADH1B and ALDH2 activity may be involved in the development of CRC.
文摘Chronic liver disease(CLD)represents a significant global health burden,with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis(MASH),alcoholic liver disease,and hepatitis C virus infection—being major contributors.Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13(HSD17B13)gene as a protective factor against the development and progression of these conditions.In this review,we summarized the current evidence surrounding the HSD17B13 rs72613567 variant,aiming to elucidate its impact on CLD risk and outcomes,and to explore the potential mechanisms behind its hepatoprotective effects.The rs72613567:TA variant induces a splice donor site mutation,resulting in a truncated,nonfunctional HSD17B13 protein.Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma(HCC)in patients with MASH,alcoholic liver disease,and hepatitis C virus infection.Moreover,the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients.Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC.Furthermore,inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH.However,the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated.Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.
文摘目的:探讨MTHFR基因C677T多态性与非综合征型唇腭裂(nonsyndromic cleft lip with or without cleft pa-late,NSCL/P)相关性。方法:收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行MTHFR基因C677T位点多态性检测;用人群关联研究、传递不平衡检验(transmission-disequlibrium test,TDT)、单倍型相对风险率(haplotype-based haplotype relative risk,HHRR)、家系为基础的关联检验(family-basedas-sociation test,FBAT)等进行统计分析。结果:人群关联研究分析表明,子代、父亲、母亲的病例组和对照组之间基因型和等位基因的分布差异无统计学意义(P>0.05);子代、父亲、母亲组,CT基因型携带者相对于CC基因型携带者的OR分别为1.02(95%CI0.47~2.21)、0.62(95%CI0.29~1.32)、0.66(95%CI0.31~1.40);TT基因型携带者相对于CC基因型携带者的OR分别为1.10(95%CI0.44~2.74)、0.95(95%CI0.39~2.32)、0.68(95%CI0.28~1.66);T相对于C基因的OR分别为1.07(95%CI0.72~1.58)、0.98(95%CI0.66~1.46)、0.83(95%CI0.56~1.24)。携带有突变基因T并不能增加患NSCL/P的危险。病例组核心家庭分析表明,TDT检验χ2=1.817,P>0.05;HHRR检验χ2=1.76,P>0.05;FBAT检验Z=1.348,P>0.05。结论:没有发现MTHFRC677T多态性和NSCLP无关联性,该基因位点的变异可能不会导致中国东北地区人群NSCLP的发生。