慢加急性乙型肝炎肝衰竭患者外周血IFN-γ基因多态性分析及其临床意义探讨*

目的 探讨乙型肝炎病毒感染引起的慢加急性肝衰竭患者血IFN-γ基因多态性。方法 采用单核苷酸多态性（SNP）技术检测51例ACLF患者和50例健康人血IFN-γ基因内含子+874 位点T/A 和+2109位点A/G单核苷酸多态性。结果 ACLF患者+874位点TA+AA基因型频率（54.9%）显著高于健康人（24.0%）,A等位基因频率（38.2%）显著高于健康人（22.0%,P<0.05）;ACLF组+2109位点AG+GG型基因型频率（51.0%）显著高于健康人（26.0%）,G等位基因（32.4%）显著高于健康人（16.0%,P<0.05）;在3 m末,28例生存与23例死亡的ACLF患者+874、+2109位点等位基因和基因型频率分布无显著性差异（P>0.05）。结论 IFN-γ基因+874 位点A等位基因和基因型、+2109位点G等位基因和基因型是ACLF的遗传易感基因。     

乙醛脱氢酶2基因多态性与老年冠心病的相关性

目的探讨乙醛脱氢酶2(ALDH2)基因G487A多态性与老年冠状动脉粥样硬化性心病(CHD)患者的关系。方法 320例行冠状动脉造影的老年患者,根据造影结果分为CHD组169例和非CHD组(对照组)151例,利用多聚酶链反应技术,检测ALDH2基因G487A多态性。结果基因型频率符合Hardy-Weinberg平衡;CHD组AA+AG基因型(ALDH2*2/*2+ALDH2*1/*2)频率明显高于GG型(ALDH2*1/*1)组,与对照组有显著性差异(P=0.011);Logistic回归分析显示,A等位基因、低HDL-C增加了CHD的危险,A等位基因、低HDL-C对CHD的发生有协同作用。结论 ALDH2基因G487A多态性与老年冠心病的发病有关,A等位基因可能是CHD发病的遗传危险因素之一。     

肝细胞癌患者IL-18基因-137G/C和-607A/C位点单核苷酸多态性变化及其意义探讨*

目的 探讨肝细胞癌（HCC）患者白细胞介素-18（IL-18）基因-137G/C和-607A/C位点单核苷酸多态性（SNP）的变化。方法 在178例伴有HBV感染的HCC患者和251例健康人,取外周静脉血提取DNA,采用聚合酶链反应-连接酶检测反应（PCR-LDR）行基因分型,测定IL-18基因-137G/C和-607A/C位点SNP。结果 HCC患者和健康人IL-18-37 G/C基因GG基因型、GC基因型和CC基因型分布频率分别为75.3%对47.0%（P<0.05）、20.8%对51.4%（P<0.05）和3.9%对1.6%（P>0.05）,G等位基因和C等位基因分布频率分别为93.6%对72.7%（P<0.05）和6.4%对27.3%（P<0.05）;HCC患者和健康人IL-18-607A/C位点AA基因型、AC基因型和CC基因型分布频率分别为37.6%对13.5%（P<0.05）、43.3 %对66.9%（P<0.05）和19.1%对19.5%（P>0.05）,A等位基因和C等位基因分布频率分别59.3%对47.0%（P<0.05）和40.7%对53.0%（P<0.05）;HCC组IL-18-137G/C位点的GG基因和G等位基因频率显著高于健康人（P<0.05）,HCC组IL-18-607A/C位点的AA基因和A等位基因频率也显著高于健康人（P<0.05）,提示携带IL-18-137G/C和IL-18-607A/C位点基因型和A等位基因者罹患HCC的风险增加。结论 携带IL-18基因-137G/C位点GG基因型和G等位基因以及-607A/C位点AA基因型和A等位基因者可能更容易发生HCC,对HBV感染者筛查这些基因可能有助于早期发现肝肿瘤,以利于早期处理和改善预后。     

乙醛脱氢酶基因多态性与酒精性肝病的关系

目的 观察乙醛脱氢酶(ALDH)基因多态性与山东地区汉族人群酒精性肝病的关系,探讨酒精性肝病遗传学的发病机制。 方法 采用聚合酶链反应结合内切酶酶切及电泳技术,检测山东地区汉族人群中酒精性肝病组、嗜酒组和对照组(各20例)中ALDH各基因型及等位基因的频率并进行比较。结果ALDH2*1、ALDH2*2两种等位基因在对照组与酒精性肝病组之间的分布差异有显著性(x2=4.80,P<0.05),对照组与无肝病嗜酒组之间差异无显著性,在嗜酒组和酒精性肝病组中以ALDH2*1/*1基因型为主,均未检出纯合子的ALDH2*2/*2。 结论 ALDH基因多态性与酒精性肝病的发生关系密切。等位基因ALDH2*2可能是本地区汉族人群中嗜酒和酒精性肝病的负性危险因素。     

慢加急性乙型肝炎肝衰竭患者血清IFN-γ基因多态性分析

目的 探究慢加急性乙型肝炎肝衰竭(HBV-ACLF)患者血清γ-干扰素(IFN-γ)基因多态性分布特点。方法 2017年5月～2019年9月我院收治的HBV-ACLF患者60例,另选择同期健康体检者60例作为对照。采用Taqman探针荧光定量PCR法检测外周血IFN-γ基因多态性位点+874T/A和+2109A/G基因型,采用x²检验和Hardy-Weinberg平衡检验IFN-γ基因SNP位点+874T/A和+2109A/G基因型和等位基因频率分布差异。结果 在IFN-γ+874T/A位点,ACLF患者TT基因型为48.3%,显著低于健康人的56.7%,而AA基因型为31.7%,显著高于健康人的13.3%(P＜0.05),在等位基因频率分布方面,ACLF患者T等位基因频率为58.3%,显著低于健康人的71.7%,而A等位基因频率为41.7%,显著高于健康人的28.3%(P＜0.05);在IFN-γ+2109A/G位点,ACLF患者显性等位基因纯合子AA基因型频率为53.3%,显著低于健康人的66.7%,隐性等位基因纯合子GG基因型频率为28.3%,显著高于对照组的10.0%(P＜0.05),在等位基因频率分布方面,ACLF患者A等位基因频率为62.5%,显著低于对照组的78.3%,而G等位基因频率为37.5%,显著高于对照组的21.7%,差异具有统计学意义(P＜0.05)。结论 IFN-γ基因多态性与乙型肝炎患者发生ACLF可能存在某种关系,其中IFN-γ基因+874T/A位点中的A等位基因和+2109A/G位点中的G等位基因可能是患者发生HBV-ACLF的风险等位基因,监测外周血IFN-γ基因多态性对及时准确地预测ACLF的发生可能具有一定的临床意义。     

汉族人群乙型肝炎病毒感染者外周血IL-28B基因多态性研究*

目的 分析乙型肝炎病毒（HBV）感染者外周血IL-28B基因型和等位基因频率分布,并探讨其与疾病病程和进展的关系。方法 本研究纳入江苏籍汉族健康人群145例和453例HBV感染者,后者包括无症状HBV携带者（ASC）45例,慢性乙型肝炎患者（CHB）181例,肝硬化（LC）患者69例,肝细胞癌（HCC）患者79例,乙型肝炎肝衰竭（LF）患者79例,采用PCR法和直接测序法检测外周血IL-28B基因rs12979860和rs8099917多态性位点。采用Pearson x²检验对IL-28B rs8099917与rs12979860位点进行Hardy-Weinberg平衡检验,计量资料以（x±s）表示,计数资料采用例数表示。应用SPSS 17.0软件进行方差分析、x²检验和Binary Logistic回归分析。结果 IL-28B基因rs12979860位点有CC、CT和TT 3个基因型,LF患者CC型和C等位基因频率分别为96.2%和98.1%,显著高于健康人群的87.6%和93.1%（OR=0.257,95%CI=0.068~0.973,P=0.045;OR=0.255,95%CI=0.070~0.928,P=0.038）;IL-28B基因rs8099917位点有TT 、TG和GG 3个基因型,LC患者TT型和T等位基因频率分别为92.8%和96.4%,显著高于健康人群的86.2%和92.4%（OR=0.288,95%CI=0.087~0.948,P=0.041;OR=0.299,95%CI=0.096~0.926,P=0.036）。结论 江苏地区汉族人群IL-28B基因多态性与HBV感染后不同疾病表型相关,IL-28B基因rs12979860的C等位基因和IL-28B基因rs8099917的T等位基因可能是HBV感染后病情进展的影响因素。     

甘肃地区ApoE与SLCO1B1基因多态性及基因型与血脂水平的相关性

目的 了解甘肃地区SLCO1B1和ApoE基因的分布特征及基因型对血脂水平的影响。 方法 采用横断面研究,对甘肃省人民医院心内科的386名患者采用聚合酶链反应进行基因多态性分析并检测其入院血脂水平,统计不同基因型的分布特征,探讨基因多态性与血脂水平的相关性。 结果 与血脂正常组相比较,血脂异常组年龄年轻、体质量指数（BMI）显著增大、TC、TG和LDL-C水平显著升高。SLCO1B1基因型*1b/*1b、*1a/*1b分别占比:42.5%、35.8%,其次是*1b/*15（10.9%）、*1a/*1a（5.4%）、*1a/*15（4.2%）、*15/*15（1.3%）,但未检测到*1a/*5、*5/*5、*5/*15基因型。SLCO1B1基因等位基因*1a、*1b、*15占比分别为:25.4%、65.8%、8.8%。388A > G与521T > C突变频率分别为74.6%、8.8%,正常与异常血脂水平组SLCO1B1基因型、等位基因分布差异未见统计学差异。ApoE基因型E3/E3、E3/E4分别占比:74.9%、15.5%;其次是E2/E3（6.7%）、E4/E4（1.3%）、E2/E4（1.0%）、E2/E2（0.5%）;等位基因ε2、ε3、ε4分别占比:4.4%、86.0%、9.5%;正常与异常血脂水平组ApoE基因型、等位基因分布差异未见统计学差异。单因素分析、多因素分析及Pearson相关性分析表明SLCO1B1、Apoe基因型与血脂水平无相关性。 结论 SLCO1B1、APOE基因多态性对血脂水平无相关性。      

山东省汉族乙醛脱氢酶2基因多态性与急性心肌梗死的相关性

目的研究山东省汉族人群乙醛脱氢酶2(ALDH2)基因G504A多态性与急性心肌梗死(AMI)的相关性。方法采用聚合酶链式反应扩增目的片段,检测山东省汉族AMI住院患者106例及汉族非冠心病对照212例ALDH2基因G504A多态性,分析比较其对AMI发病的影响。结果①病例组突变型ALDH2(ALDH2*1/*2,ALDH2*2/*2)明显高于对照组(P0.05)。②Logistic多元回归校正BMI、高血压、糖尿病、吸烟史以及TC、TG、HDL-C、LDL-C等因素后,突变型ALDH2基因患者发生AMI风险为野生型组的1.97倍(P=0.04);③纳入饮酒史这一因素后,突变型ALDH2基因与急性心肌梗死的发生仍然相关(OR=2.00,P0.01),HDL-C水平则成为一种保护性因素(OR=0.50,P0.01)。结论 ALDH2基因G504A多态性是山东省汉族人群发生急性心肌梗死的独立危险因素,其作用可能与其调节HDL-C水平有关。     

1型糖尿病并发慢性胆囊炎患者外周血IL-6基因多态性研究

目的 分析外周血IL-6 174C/G基因型和等位基因频率在研究人群中的分布情况,以探讨1型糖尿病（T1DM）并发慢性胆囊炎患者外周血IL-6基因多态性的变化。方法 收集1型糖尿病并发慢性胆囊炎患者110例和健康对照者120例。采用聚合酶链反应-限制性片段长度多态性法对所有受检者进行外周血基因多态性检测,计算基因型频率和等位基因频率,并结合问卷调查和临床生化检查的相关信息进行病例对照分析研究。应用SPSS 17.0统计软件包行统计分析。结果 纳入本研究的两组人群性别和年龄具有可比性,1型糖尿病并发慢性胆囊炎患者体质指数（BMI）为（28.15±3.98） kg/m2,显著高于健康人的（26.86±6.52） kg/m2（P＜0.05）;在110例1型糖尿病并发慢性胆囊炎患者中,伴有高血压现患例数65例（59.09%）,显著高于健康人的32.50%（39/120,P＜0.01）; 1型糖尿病并发慢性胆囊炎患者存在糖尿病家族史的比例显著高于健康人（54.55%对10.83%,P＜0.01）; 1型糖尿病并发慢性胆囊炎患者吸烟（13.64%）和饮酒（19.09%）史的比例显著高于健康人（分别为11.67%和8.33%,P＜0.01）;1型糖尿病并发慢性胆囊炎患者外周血IL-6 174C/G基因CC基因型为40.91%,显著高于健康人的28.33%（P＜0.05）,而GG基因型为7.27%,显著低于健康人的19.17%（P＜0.05）,C等位基因分布为52.73%,显著高于健康人的15.00%（P＜0.01）;单因素分析结果提示,携带IL-6 174 C等位基因【（OR=1.357(1.037～1.776),P＜0.05】、存在高血压现病【OR=1.324（1.187～1.476）,P＜0.01】、肥胖【OR=1.165（1.087～1.249）和有饮酒史【OR=1.113（1.046～1.184）,P＜0.01】为T1DM患者并发胆囊炎的危险因素;多因素Logistic回归分析结果提示携带IL-6 174 C等位基因【OR值及其95%可信区间分别为1.258（1.119～1.413）】、高血压【1.225（1.032～1.454）】和肥胖【1.167（1.056～1.289）,P＜0.01】以及饮酒史【OR值为1.111（1.006～1.228）,P＜0.05】为T1DM患者并发胆囊炎的独立危险因素。结论 IL-6 -174C/G基因多态性与1型糖尿病患者并发胆囊炎的易感性有相关关系。     

乙醛脱氢酶2基因 rs671多态性和新疆汉族人群原发性高血压的关联性研究

目的：探讨乙醛脱氢酶2（ALDH2）基因 rs671多态性在新疆地区汉族人群原发性高血压（EH）发病中的作用。方法应用 Taqman 技术检测了474例汉族 EH 患者和358例正常血压者 ALDH2基因 rs671多态性。结果在男性人群中,饮酒组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于不饮酒组（P ＜0．01）;EH 组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于对照组（P ＜0．01）。而在女性人群中,EH 组和对照组 rs671的 3 种基因型频率和等位基因频率的分布差异无统计学意义（P ＞0．05）。非条件 Logistic 回归分析校正年龄、体重指数、糖尿病史、饮酒史等影响因素后,在男性人群中 rs671的 GA ＋AA 基因型者患 EH 的风险低于 GG基因型者（OR ＝0．656,95％CI：0．448～0．962,P ＜0．05）,GA ＋AA 基因型者收缩压水平明显低于GG 型者（P ＜0．05）。而在男性不饮酒者和女性人群中,GA ＋AA 基因型者和 GG 基因型者血压水平比较差异无统计学意义。结论ALDH2基因 rs671多态性可能和新疆汉族男性人群 EH 的发生相关,rs671的 GA ＋AA 基因型可能是汉族男性人群 EH 的一个保护因素。     

Genetic polymorphisms of ADH2 and ALDH2 association with esophageal cancer risk in southwest China

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     

Polymorphism of Alcohol-Metabolizing Genes Affects Drinking Behavior and Alcoholic Liver Disease in Japanese Men

Alcohol is known to be mainly metabolized in the liver by alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2), and cytochrome P-45011EI. The purpose of this study was to clarify the role of polymorphism of these ethanol-metabolizing enzymes in drinking behavior and the progression of alcoholic liver disease among Japanese men. Polymorphism of the ADH2, ALDH2, and P-45011EI genes was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis in 189 normal Japanese men and 26 male patients with alcoholic liver disease. Drinking behavior was estimated by self-assessment according to DSM-Ill-R criteria. Facial flushing was reported in 91 subjects heterozygous for ALDH2*1/*2 and in two subjects homozygous for ALDH2*2/*2, but was not found in 96 subjects homozygous for ALDH2*1/*1. In contrast, polymorphism of ADH2 and P-45011EI did not differ between flushers and nonflushers. Although the flushers only drank a small amount of alcohol (<20 g of ethanoVday), the nonflushers were divided into a group of moderate drinkers (20 to 80 glday; n = 54) and a group of heavy drinkers (780 g/day; n = 42). A high preponderance of heterozygosity for the ADH2*1/*2 genes (29/ 42; 69%) and a high frequency of the ADH2*1 allele were found in heavy drinkers, compared with moderate drinkers. However, cytochrome P-45011EI gene polymorphism was similar among the moderate and heavy drinkers. Not only a high frequency of the ALDHPl and ADH2*1 alleles, but also a high frequency of the P-45011EI c2 allele was found in the patients with alcoholic liver disease. From these results, the drinking behavior of Japanese men is strongly influenced by the ALDH2*l allele, and the level of alcohol intake is affected by the ADH2*1 allele, but not by cytochrome P-45011EI. However, progression to alcoholic liver disease among heavy drinkers may be affected by the cytochrome P-45011EI c2 allele.     

Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

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/＊     

Self-Reported Alcohol-Associated Symptoms and Drinking Behavior in Three ALDH2 Genotypes Among Japanese University Students

BACKGROUND: Alcohol abuse is one of the most serious health problems among young adults. Nearly half of the Japanese population is sensitive to alcohol due to a genetic polymorphism in low K(m) aldehyde dehydrogenase (ALDH2). In the present study, we investigated the effects of the ALDH2 genotype on both self-reported alcohol-associated symptoms and alcohol drinking behavior among Japanese university students. METHODS: The study subjects were 423 (389 males and 34 females) university students in a medical university. The subjects completed a questionnaire regarding self-reported alcohol-associated symptoms and alcohol drinking behavior. The ALDH2 genotype was determined through digestion of polymerase chain reaction (PCR) products by a restriction enzyme Ksp632I. The frequency of alcohol-associated symptoms generally increased in the order ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2 among males. The frequency of those who drink > or = 5 days/week was less than 10% in all genotype groups. However, the frequency of those who drink 1-4 days/week was significantly higher in ALDH2*1/*1 than that in ALDH2*1/*2 and in ALDH2*2/*2. A similar tendency also was observed in females. Mean amounts of alcohol consumption per occasion in the three ALDH2 genotypes stratified by drinking frequency generally increased significantly in the order ALDH2*2/*2, ALDH2*1/*2, ALDH2*1/*1 in both sexes. The proportion of binge drinkers defined by those who drink ethanol of > or = 75 ml per occasion on average also increased in the order ALDH2*2/*2 (0.0%), ALDH2*1/*2 (9.8%), ALDH2*1/*1 (22.1%) among male drinkers (> or = 1 day/month). CONCLUSIONS: We for the first time demonstrated clear associations between the ALDH2 genotype, self-reported alcohol-associated symptoms, and alcohol drinking behavior among Japanese university students.     

老年人乙醛脱氢酶2基因多态性与高血压病的关系

目的：探讨乙醛脱氢酶2（ALDH2）基因多态性与老年高血压病的关系。方法：111例老年人分为高血压病组（80例）与非高血压对照组（31例）,对比两组间ALDH2基因多态性。利用DNA微阵列芯片法检测ALDH212号外显子上基因的G to A突变（导致第504位氨基酸Glu被Lys取代）。结果：本研究检测出三种ALDH2基因型,包括ALDH2野生型（ALDH2＊1/＊1）,ALDH2突变杂合型（ALDH2＊1/＊2）,ALDH2突变纯合子型（ALDH2＊2/＊2）。与非高血压对照组相比,高血压病组的野生型,ALDH2＊1等位基因（54.8%比66.3%,74.2%比82.5%）比例增多,但差异无显著性,而突变型、ALDH2＊2等位基因比例减少（45.2%比33.8%,25.8%比17.5%）,差异亦无显著性（P均〉0.05）;高血压组男性亚组的野生型、ALDH2＊1等位基因比例增多（54.2%比67.2%,72.9%比83.6%）,差异亦无显著性（P〉0.05）。结论：乙醛脱氢酶2基因多态性与老年人高血压病可能不相关。     

Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population.

In Japanese and other Asians, the prevalence of genetically decreased mitochondrial aldehyde dehydrogenase (ALDH2) activity is higher than in Caucasians. The aim of this study was to elucidate the relation between ALDH2 genotypes and blood pressure levels or hypertension in Japanese. After obtaining informed consent for genetic analysis from 917 men and 1,478 women who lived in a mountainous farming region near Kyoto and who were free from cardiovascular disease and liver dysfunction, the authors identified the ALDH2 genotype in all subjects. Differences in blood pressure level among genotypes were then compared by analysis of covariance, and the relation between genotypes and hypertension was also analyzed by logistic regression analysis. The frequencies of genotypes *1/*1, *1/*2, and *2/*2 were 44.7%, 46.9% and 8.4% in men, and 50.1%, 43.2% and 6.8% in women, respectively. In men, systolic and diastolic blood pressures tended to decrease in the order of *1/*1>*1/*2>*2/*2. However, adjustment for confounding factors including alcohol consumption resulted in the disappearance of significance. Logistic regression analysis adjusted for the same confounding factors for men showed that the odds ratios (OR) of being hypertensive in the *2 allele to not having *2 allele were 0.67 (95% confidence interval (CI): 0.47-0.96). However, in the subgroup analyses, this relation was not observed in the group having a below-median level of alcohol consumption (OR = 0.92; 95% CI: 0.53-1.62) or in the group not taking antihypertensive agents (OR = 0.77; 95% CI: 0.52-1.15). Furthermore, we did not observe any relation between the ALDH2/*2 allele and hypertension in women (OR = 1.07; 95% CI: 0.80-1.42). The results suggest that there may be no causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking.     

Esophageal squamous cell carcinoma and aldehyde dehydrogenase-2 genotypes in Japanese females

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) is the key enzyme for elimination of acetaldehyde, an established animal carcinogen produced after drinking. In persons with inactive ALDH2, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Inactive heterozygous ALDH2 enhances the risk of esophageal squamous cell carcinoma (SCC) in Japanese male drinkers. METHODS: We studied whether this is the case for women. The risk factors of esophageal SCC were examined in 52 Japanese women with esophageal SCC and 412 cancer-free Japanese women. RESULTS: The increasing trend in cancer risk according to the quantity of alcohol consumption was significantly steeper in women with inactive heterozygous ALDH2 than in those with active ALDH2 [adjusted odds ratios (ORs) (95% confidence intervals (CIs)) per +7 U/wk increment of alcohol drinking were 3.91 (2.09-7.31) and 1.39 (0.92-2.09), respectively; p = 0.006 for difference in OR; 1 Ut = 22 g of ethanol]. The results obtained using an alcohol-flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87-8.31) and 1.46 (0.96-2.23) in those with and without flushing, respectively; p = 0.021 for difference in OR]. The risk of esophageal cancer was markedly higher in heavy drinkers with ALDH2*1/*2 than in never/rare drinkers with ALDH2*1/*1 [adjusted OR (95% CI) = 59.1 (4.65-750)]. Other independent significant risk factors of esophageal SCC were smoking, a preference for hot food or drinks, and lower intake of green and yellow vegetables. CONCLUSIONS: Japanese men and women shared several common risk factors of esophageal SCC, including drinking with inactive heterozygous ALDH2.     

Effects of alcohol intake and low Km aldehyde dehydrogenase on hepatic function in a high hepatitis C virus-prevalent Japanese island population

In Asians from the Pacific rim countries, alcohol sensitivity has been attributed mainly to a highly prevalent polymorphism in low Km aldehyde dehydrogenase (ALDH2). Chronic alcohol abuse may accelerate or aggravate the liver injury in chronic hepatitis C virus (HCV)-infected subjects. In this study, we examined the relationships among alcohol intake, ALDH2 genotypes, and liver injury in a high HCV-prevalent Japanese native island population. The ALDH2 genotypes are significantly associated with drinking habits. In HCV RNA positive subjects, serum alanine aminotransferase (ALT), as well as aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT), were significantly higher in habitual drinkers than in nonhabitual drinkers. In male habitual drinkers, the ALDH2*1/*1 subjects had higher liver necroinflammatory scores than the ALDH2*1/*2 subjects in all groups classified as: I, anti-HCV-seronegative; II, anti-HCV-seropositive with negative HCV RNA; and III, HCV RNA positive, although scores for the latter two groups were not statistically significant because of limited sample size. It was suggested that the liver function might be affected by the interaction between the ALDH2 genotypes and alcohol intake. These findings indicate that HCV-infected ALDH2*1/*1 habitual drinkers are the major target for the prevention of alcoholic liver diseases.     

Mean corpuscular volume and the aldehyde dehydrogenase-2 genotype in male Japanese workers

BACKGROUND: Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH2*1/2*2 have very high risks for esophageal cancer, MCV might serve as an indicator of these high-risk drinkers. METHODS: In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses. RESULTS: Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (>or=9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH2*1/2*2 than in those with ALDH2*1/2*1. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH2*1/2*2 than for those with ALDH2*1/2*1, demonstrating a gene-environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH2*1/*2*2 but for only 1.3% of variance among those with ALDH2*1/2*1. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH2*1/2*2 and ALDH2*1/2*1, respectively. Macrocytosis (MCV >or=100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH2*1/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152). CONCLUSIONS: Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde's role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer.