ADH1B与ALDH-2基因多态性与中国人群食管癌发病风险的Meta分析

目的探讨中国人乙醇脱氢酶1B(ADH1B)和乙醛脱氢酶-2(ALDH-2)的基因多态性与食管癌发病风险的关系。方法检索中外文数据库,获得有关ADH1B和ALDH-2位点的多态性与食管癌发病风险的病例-对照研究资料,对各位点以及与饮酒的交互作用进行Meta分析,得到合并的OR值及其95%CI。结果等位基因ADH1B*1和ALDH-2*2可增加食管癌的发病风险。基因型ADH1B*1/*2和ADH1B*1/*1的OR值分别为1.24(95%CI 1.10-1.41)和3.05(95%CI 1.94-4.77);基因型ALDH-2*1/*2和ALDH-2*2/*2的OR值分别为1.6(95%CI 1.01-2.03)和0.77(95%CI 0.28-2.09)。在饮酒人群中,与基因型ADH1B*2/*2相比,ADH1B*1/*2+*2/*2的OR=3.13(95%CI 2.17-4.51);与基因型ALDH-2*1/*1相比,ALDH-2*1/*2+*2/*2的OR=4.12(95%CI 1.98-8.56)。结论在中国人群中,等位基因ADH1B*1和ALDH-2*2均能增加食管癌患病的风险,且饮酒可以增加这一风险。     

ADH2、ALDH2基因多态性及饮酒和胃癌关联的研究

[目的]探讨乙醇脱氢酶2(ADH2)、乙醛脱氢酶2(ALDH2)基因多态性及饮酒和胃癌的联系。[方法]采用病例对照研究的方法,利用变性高效液相色谱法(DHPLC)检测常熟市201例男性原发性胃癌患者和对照组ADH2、ALDH2基因型,结合饮酒因素分析其在胃癌发生中的作用。[结果]与携带ADH2(A/A)或ALDH2(G/G)基因型者相比,其它基因型并不增加患胃癌的危险性(P0.05),结合ADH2、ALDH2基因多态性及饮酒因素发现,即使饮酒量超过1.5 kg.年饮酒者任何基因型组合和不饮酒者携带ADH2(A/A)或ALDH2(G/G)基因型者相比,患胃癌的危险性并未增加(P0.05)。[结论]ADH2、ALDH2基因多态性与胃癌易感性无关。     

ALDH2和CYP2E1基因多态性及饮酒习惯与肝细胞癌易感性的关系

目的研究乙醛脱氢酶2(ALDH2)和细胞色素P4502E1(CYP2E1)基因多态性与饮酒因素交互作用在广西原发性肝细胞癌发生中的作用。方法对广西壮族自治区300例肝细胞癌和292例正常对照进行流行病学调查研究,并用PCR-RFLP方法检测ALDH2和CYP2E1基因型。结果病例和对照组中ALDH2和CYP2E1变异基因型携带者分别占50.3%、48.0%和32.3%、32.9%(P0.05)。饮酒频度每周≥3次(高频饮酒)且携带变异基因ALDH2和CYP2E1者发生肝癌的危险度分别是饮酒频度每周3次(低频饮酒)且携带野生基因型者的3.334倍(95%CI=1.746～6.406)和1.803倍(95%CI=0.974～3.336),同时携带两变异基因型者患肝癌风险为1.200倍(95%CI=0.730～1.972),且饮酒增加两变异基因型携带者的肝癌发病风险(OR=1.816,95%CI=0.985～3.348)。结论单一ALDH2或CYP2E1基因型与肝细胞癌易感性无关;但高频饮酒且携带变异基因ALDH2或CYP2E1者患肝癌风险增加,且两变异基因型单倍体增加肝癌发病风险。提示乙醇在增加肝癌发病风险的过程中存在基因-环境和基因-基因相互作用。     

浙江汉族人群ALDH2(Glu504Lys)基因多态性与高血压的相关性

目的 研究乙醛脱氢酶2(ALDH2)基因的第504位点(Glu504Lys)多态性与汉族人群高血压的相关性.方法 将465名汉族人(无亲缘关系)分为2组,高血压组105例与非高血压组360人,采用基因芯片法比较两组ALDH2基因型的分布频率是否存在差异.结果 465名汉族人的ALDH2的基因型有3种,ALDH2野生纯合子型(ALDH2*1/*1)、ALDH2突变杂合型(ALDH2*1/*2)和ALDH2突变纯合子型(ALDH2* 2/ *2),高血压组例数和比例分别是73例(69.52％)、30例(28.57％)和2例(1.90％),非高血压组209人(58.05％)、139人(38.61％)和12人(3.33％),这3种基因型在所检测人群中的分布符合Hardy-Weinberg定律(P＞0.05).统计学分析发现,高血压组的ALDH2*1/ *1基因型(69.52％)高于非高血压组(58.05％),差异有统计学意义(P＜0.05).结论 浙江汉族人群的乙醛脱氢酶2基因多态性与高血压的发生关系密切.     

AS-PCR在ADH2、ALDH2基因多态型分析中的应用

[目的]为获得更为简便经济同时精确度足够高的酒精脱氢酶2(ADH2)和乙醛脱氢酶2(ALDH2)基因多态型测定的新方法。[方法]建立并优化等位基因特异性PCR(alle lespecific-PCR，AS-PCR)方法，通过与经典HCR-RFIP方法的分型结果相比较考察其可行性。[结果]AS-PCR方法对60例DNA样本的ADH2、ALDH2基因的分型结果与PCR-RFLP法完全一致，且简便快速，成本低，特异性和准确度也足够高。[结论]AS-PCR方法分析ADH2、ALDH2基因多态型优点明显，尤其适于基层以及大规模调查应用。     

ALDH2基因多态性与男性饮酒行为关系的分子流行病学研究

目的 探讨乙醛脱氢酶基因(acetaldehyde dehydrogenase gene 2,ALDH2)多态性与男性饮酒行为的关系.方法 采用TaqMan对823名正常男性ALDH2的9个标签单核苷酸多态性位点(single-nucleotide polymorphism,SNP)进行分型,使用Logistic回归分析基因型与饮酒行为的关系.结果 调整年龄、受教育、婚姻、收入和吸烟后,5个SNP与饮酒行为的关联具有统计学意义(rs671 (G＞ A),OR=0.35,95％ CI:0.27～0.45,P＜0.001;rs2283354(G＞A),OR =1.61,95％ CI:1.26 ～2.05,P＜0.001;rs4767939(G＞A),OR=1.46,95％ CI:1.01 ～2.11,P=0.042;rs79073142(T＞C),OR=1.71,95％ CI:1.37 ～2.14,P＜0.001;rs2106696(A ＞T),OR=1.75,95％ CI:1.40 ～2.19,P＜0.001).携带危险等位基因个数越多,发生饮酒行为的可能性越高(趋势性P值＜0.001).SNP两两之间的交互效应没有统计学意义.结论 ALDH2基因多态性可影响中国男性饮酒行为.     

CYP4502E1基因多态型对青海藏族男性饮酒行为的影响

目的分析细胞色素P450 2E1(CYP450 2E1)不同基因型及等位基因频率,探讨其与藏族男性饮酒行为之间的关系。方法采用自评式问卷,对325名藏族男性进行调查分析,其中饮酒者193人,不饮酒者132人,另选取266名汉族男性作为对照,采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)对基因的多态型进行分析,探讨其与饮酒行为之间的相关性。结果不同职业﹑文化程度﹑经济收入﹑婚姻情况﹑吸烟情况人群组中的饮酒率差异具有显著性(P<0.05)。藏汉族男性基因型及等位基因频率分布差异无显著性(P>0.05)。藏族男性饮酒组和不饮酒组比较,CYP450 2E1三种基因型c1/c1、c1/c2和c2/c2的分布差异具有显著性(χ2=10.101,P<0.05),c1/c2基因型频率在饮酒组比在不饮酒组中的高;c1和c2两个等位基因分布差异也具有显著性(χ2=9.223,P<0.05),c2等位基因频率在饮酒组也比在不饮酒组中的高,与安全饮酒相比,危险饮酒组中c2等位基因频率更高。c2等位基因与是否饮酒以及饮酒量的关联程度分别为0.17和0.20。多因素分析显示:影响饮酒行为的因素依次为CYP450 2E1基因、吸烟和经济收入。结论CYP450 2E1基因是影响藏族男性饮酒行为的主要因素。     

青海部分地区藏、汉族男性人群饮酒行为模式分析

目的了解青海地区藏、汉族男性饮酒行为模式。方法采用系统抽样、整群抽样等方法抽取在青海省疾病预防控制中心门诊、青海省藏医院及青海大学医学院共抽取研究对象732人,其中藏族430人,汉族302人。征得同意后对研究对象进行相关饮酒行为的问卷调查。结果藏、汉族的整体饮酒率分别为66.47%和69.54%;藏、汉族人群中安全饮酒者分别占39.07%和41.39%,危险饮酒者分别占27.67%和28.16%;藏、汉族均以低度白酒为主分别占67.94%和64.28%;藏、汉族饮酒者中饮酒方式以众饮佐菜为主分别占79.44%和58.09%。结论藏、汉族男性的饮酒率高,饮酒者年轻化,饮酒人群中仍存在不安全饮酒行为。健康工作者更加需要注意那些处于危险边缘的危险饮酒者和有害饮酒者,如果该危险饮酒者和有害饮酒者还没有发展到酒依赖的程度,能够早期及时的采取干预,能够有效的减少酒量和酒精所致的问题。     

中国南方客家人群乙醛脱氢酶2基因多态性与急性心肌梗死的相关性研究

目的探讨中国南方客家人群中乙醛脱氢酶2基因(ALDH2)Glu504Lys多态性与急性心肌梗死(AMI)之间的关系。方法本研究共纳入2016年5月至2018年5月在梅州市人民医院就诊AMI患者252例及同期健康体检者264例,提取外周血基因组DNA,通过聚合酶链反应(PCR)和DNA微阵列芯片法检测ALDH2 Glu504Lys基因多态性。结果 AMI组ALDH2 GG、GA和AA基因型所占比例分别为45.63%、44.05%和10.32%,G和A等位基因频率分别为67.66%和32.34%。对照组ALDH2GG、GA和AA基因型所占比例分别为56.82%、35.98%和7.20%,G和A等位基因频率分别为74.81%和25.19%。ALDH2基因型和等位基因频率的分布在两组间差异有统计学意义,其中A突变等位基因携带者在AMI组的比例较高(P<0.05)。Logistic回归分析显示,年龄、性别、饮酒、高血压病、糖尿病、高脂血症是AMI的危险因素。此外,ALDH2 GA/AA基因型是中国南方客家人群AMI发生的独立危险因素(OR=1.906,95%可信区间:1.278～2.844,P=0.002)。结论 ALDH2基因Glu504Lys位点多态性可能与中国南方客家人群AMI相关,其中A等位基因可能是AMI发生的易感等位基因。     

酒精性心肌病与ADH3基因多态性的关系

本文探讨了酒精性心肌病与醇脱氢酶ADH3基因多态性的关系。结果显示，嗜酒组和酒精性心肌病组ADH3＊1／＊2及ADH3＊2／＊2型频率高于对照组（P＜0．05），而ADH＊31／＊1型频率低于对照组（P＜0．05）。同时嗜酒组和酒精性心肌病组ADH3＊1等位基因的频率低于对照组（P＜0．05），而ADH3＊2等位基因的频率高于对照组（P＜0．05），嗜酒组和酒精性心肌病组ADH3基因型频率无统计学差异，等位基因的频率亦无统计学差异。故ADH3基因多态性与嗜酒相关，与酒精性心肌病发生的关系未得到证实，与酒精性心肌病的临床表现有一定关系。     

Blood pressure, levels of serum lipids, liver enzymes and blood glucose by aldehyde dehydrogenase 2 and drinking habit in Japanese men

Objectives The association of blood pressure and levels of serum lipids, liver enzymes, blood glucose and aldehyde dehydrogenase 2 (ALDH2) with drinking habit was examined in Japanese men. Methods The subjects were 264 men aged 39 to 80 years who were classified into the ALDH2 deficiency or sufficiency group using the ethanol patch test and the Tokyo University ALDH2 Phenotype Screening Test. A self-administered questionnaire including drinking habit was used. Blood pressure and the levels of biochemical markers in groups with ALDH2 sufficiency, ALDH2 deficiency and drinking habit were compared using multiple regression models for adjusting age, smoking habit, physical exercising habit and body mass index. Results The levels of serum high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (γ-GTP) were significantly higher in current drinkers of 20 g of ethanol or more per day than in nondrinkers of the ALDH2 sufficiency group. The levels of serum AST and γ-GTP in current drinkers of 20 g of ethanol or more per day, and fasting blood sugar in current drinkers of less than 20 g of ethanol per day were significantly higher than those in nondrinkers of the ALDH2 deficiency group. Conclusions These results suggest that alcohol consumption increases the levels of serum lipids and liver enzymes in ALDH2-sufficient individuals and liver enzymes and blood glucose levels in ALDH2-deficient individuals.     

乙醛脱氢酶2基因多态性及环境暴露与胃癌易感性

目的探讨乙醛脱氢酶2（ALDH2）基因多态性及环境暴露与胃癌易感性的关系。方法采用1：1配对病例一对照研究和扩增产物长度多态性（APLP）方法，检测南京市169例原发性胃癌患者和对照的ALDH2基因型，分析其在胃癌发生中的作用；结合环境危险因素分析，对ALDH2基因多态性与环境危险因素在胃癌发生中的交互作用进行分析。结果ALDH2基因型在病例组和对照组分布差异有统计学意义（X^2=4．617，P=0．032）。消化道疾病史、腌制食品、三餐不定时、暴饮暴食4项因素与胃癌发生的危险性增加有关；ALDH2基因与消化道疾病史、三餐不定时及暴饮暴食存在一定的交互作用。结论ALDH2基因多态性与胃癌易感性有关，并与环境暴露有一定的交互作用。关键词：乙醛脱氢酶2（ALDH2）基因；基因多态性；胃癌；易感性     

Relationships of alcohol dehydrogenase 1B (<Emphasis Type="Italic">ADH1B</Emphasis>) and aldehyde dehydrogenase 2 (<Emphasis Type="Italic">ALDH2</Emphasis>) genotypes with alcohol sensitivity,drinking behavior and problem drinking in Japanese older men

Objectives

Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan.

Methods

The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ² test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors.

Results

The frequency of ‘always’ facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.

Conclusions

We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

     

绵阳市男男性行为者饮酒行为及与艾滋病相关因素关系

目的 了解男男性行为者（MSM）饮酒行为现状,分析饮酒行为与艾滋病相关因素的关系。方法 于2012年9月-2013年3月采用滚雪球采样法,对四川省绵阳城区符合条件的MSM进行招募和相关行为学、血清学匿名调查。结果 共调查402人,有饮酒行为占44.0（177人）。其中近6个月饮酒频率每月≤1次26.0%、2~3次30.5%,每周1~2次24.3%、3~4次5.1%、5~6次3.4%、≥1次/天10.7%。多因素分析结果：文化程度越低（OR=0.352,95%CI=0.166~0.747）、近1次男性肛交无保护性（OR=3.351,95%CI=1.131~9.925）、近6月异有性性行为（OR=2.800,95%CI=1.017~7.706）、近6月肛交人数≥3人（OR=2.339,95%CI=1.003~5.453）、吸烟（OR=0.372,95%CI= 0.175~0.790）是饮酒行为高危因素。饮酒、吸烟与近6月无保护性男性肛交有交互作用（P=0.047）。结论 MSM饮酒较为普遍,饮酒行为与艾滋病高危行为相关,烟、酒有协同作用。在MSM艾滋病防治中应注重饮酒行为干预。     

Effect of acute ethanol drinking on alcohol metabolism in subjects with different ADH and ALDH genotypes

The effect of different amounts of orally ingested ethanol on plasma alcohol dehydrogenase (ADH) and erythrocyte aldehyde dehydrogenase (ALDH), as well as on the blood ethanol and acetaldehyde levels, was examined in healthy nonalcoholic subjects. The genotypes at ADH2 and ALDH2 locus were identified in enzymatically amplified blood DNA by hybridization with allele-specific oligonucleotides. While the Japanese subject was found to be genotypically heterozygous for both ADH2 and ALDH2, the Caucasian subjects were genotypically homozygous normal for these alleles. A faster ethanol elimination associated with a higher blood acetaldehyde level was observed in the Japanese subject as compared to Caucasian subjects. However, no significant change in ADH and ALDH enzyme activities was detected as the result of acute ethanol intake.