易感基因在X射线工作者高血压发病中的作用探讨

目的：研究遗传易感性在X射线工作者原发性高血压发病中的作用，探讨职业因素和血管紧张素转换酶基因（ACE）及血管紧张素原基因（AGT）M235T多态性同高血压发病之间的关系。方法：问卷调查X射线工作者高血压病家族史，采用聚合酶链反应、限制性内切酶片断长度多态性的方法检测了X射线工作者ACE和M235T基因多态性，SAS6.12软件进行资料分析。结果：有家族史的高血压患者同无家族史的对照相比AGT基因M235TTT基因型和T等位基因同高血压病相关；MM、MT、TT基因型的研究对象，家族史阳性率分别为0.21、0.29和0.45（P=0.028）；担心从事放射工作有害健康的X射线工作者，AGT基因M235TTT基因型对高血压病的影响更加显著；累积剂量大于30mGy组，T等位基因频率在病例和对照组间差异有显著性（P=0.028）。结论：AGT基因M235T TT基因型是X射线工作者高血压病的遗传易感基因型；职业紧张、电离辐射等职业因素可能对遗传基因型与高血压的作用有一定的影响。     

血管紧张素原基因多态性与原发性高血压的相关性研究

目的 探讨血管紧张素原（AGT）的M235T多态性与重庆市主城区抽样人群原发性高血压的关系。方法 以人群为基础进行高血胜病例．对照研究，应用PCR-RFLP技术，分析AGT的M235T多态性。结果 病例组中TT基因型的频率高于对照组（32．05％比21．34％）。与MM基因型比较，暴露于TT基因型的OR值为3.86。病例组中T等位基因的频率也高于对照组（73％比59％），随着等位基因T的增加，患高血压的危险性也增加，趋势X^2检验P〈0．001。结论 AGT的M235T等位基因可能是重庆地区人群原发性高血压的遗传易感标记。     

AGT基因多态性及倒班与煤矿井下工人原发性高血压的关系

目的分析血管紧张素原(AGT)M235T基因多态性和倒班与原发性高血压(EH)的关系。方法选择煤矿井下接尘工人为研究对象(EH组和对照组各206人),进行职业流行病学调查,并收集研究对象空腹静脉血5ml,提取基因组DNA,采用限制性片段长度多态性(RFLP)方法检测AGT M235T的基因型。比较组间的基因型、等位基因频率及倒班分布的差异,分析基因型、等位基因频率及倒班与EH的关系。结果EH组和对照组倒班作业工人所占的比例分别为42.23%和29.61%,组间分布比较,差异有统计学意义(χ2=7.13,P<0.05);倒班使EH发生的危险增加1.74倍。AGT M235T基因MM、MT、TT基因型频率在EH组和对照组分别为8.74%、81.07%、10.19%和12.62%、83.01%、4.37%,EH组和对照组比较,差异有统计学意义(χ2=6.30,P<0.05);TT基因型发生EH的危险是MM基因型的3.37倍。EH组M和T等位基因频率分别为49.27%、50.73%,对照组分别为54.13%、45.87%,EH组和对照组比较,M等位基因频率有升高趋势,T等位基因频率有下降趋势,差异无统计学意义(P>0.05)。倒班与AGT M235T基因型和等位基因存在交互作用。结论倒班和AGT M235T基因TT基因型可能是EH的危险因素。     

AGT基因M235T多态性与原发性高血压靶器官损伤的关系研究

目的探讨AGT基因M235T多态性与原发性高血压靶器官损伤的关系。方法检测高血压肾病组、高血压左室肥厚组和原发性高血压无并发症组患者的AGT基因型频率,统计学分析比较其差异。结果高血压肾病组和高血压左室肥厚组的AGT 235MM型频率与无并发症组差异无统计学意义(P0.05),高血压肾病组AGT 235MT型和AGT235TT型频率均高于无并发症组,差异有统计学意义(P0.05),高血压左室肥厚组AGT 235MT型和AGT 235TT型,尤其TT型频率高于无并发症组,差异有统计学意义(P0.05)。结论高血压肾病和高血压左室肥厚的发生与AGT235MT型和AGT 235TT型有关。AGT 235TT型尤其容易引起高血压左室肥厚。     

家族性原发性高血压与基因多态性关系

目的 探讨山东省汉族人群鸟苷酸结合蛋白(G蛋白)β3亚单位基因(GNB3)C825T多态性和血管紧张素原(AGT)基因M235T多态性与家族性原发性高血压(EH)的关系。方法 应用聚合酶链反应(PCR)和限制性内切酶酶切方法,对162例原发性高血压患者和180名正常对照组进行GNB3 C825T和AGT M235T多态性检测。结果 EH组GNB3 C825T各等位基因频率与正常对照组比较差异无统计学意义(P>0.05);EH组AGTM235T多态性的MT+TT基因型及T等位基因频率则高于对照组,差异有统计学意义(P<0.05);在AGT TT纯合子中,GNB3 TT纯合子患病率及收缩压(SBP)、舒张压(DBP)均高于C等位基因携带者(P<0.05);逐步Logistic回归分析结果显示,825TT+235TT基因型高血压的发病危险为其他基因型的3.45倍(P=0.001),高于单基因的AGT 235TT(1.87)。结论 AGT基因M235T多态性T等位基因是山东省汉族原发性高血压家系人群EH发病的危险因素之一。GNB3 825T等位基因对高血压的发病有协同作用。     

AGT基因M235T多态性和ACE基因I/D多态性与妊娠期高血压疾病的关系研究

目的:探讨肾素-血管紧张素系统中AGT基因M235T多态性和ACE基因I/D多态性与妊娠期高血压疾病(HDCP)易感性的关系。方法:采用病例对照研究,选取安阳地区99对HDCP产妇及其对照进行问卷调查,并收集血样后运用PCR-RFLP和PCR技术分别对AGT基因M235T多态性和ACE基因I/D多态性进行检测鉴别。结果:经统计分析发现,病例和对照组的孕周、文化程度、职业和肥胖程度差异有统计学意义(P0.05)。两组孕妇AGT基因及ACE基因型均无显著差异(P0.05)。结论:未发现AGT基因M235T多态性和ACE基因I/D多态性与HDCP易感性有关联。     

克拉玛依油田工人职业紧张与ADD1基因对高血压患病率的影响

[目的]探讨克拉玛依油田工人职业紧张和ADD1基因对高血压患病率的影响。[方法]采用随机整群抽样方法抽取克拉玛依某油田在岗作业工人1 300人,运用职业紧张量表进行问卷调查(回收有效问卷1 233份,问卷有效率为94.8%),采集其中352名油田工人(高血压病例组和非高血压对照组各176人)的血样,并提取DNA,运用聚合酶链式反应-限制性片段长度多态性技术检测ADD1基因rs17833172和rs4961位点的基因型。[结果]1 233名油田工人的职业任务得分(168.28±34.19)高于国内常模(162.89±27.04)(P0.05),且高血压患病率随紧张程度增加而上升(χ_(趋势)~2=13.82,P0.05),高度紧张组的高血压患病率(18.49%)高于低度紧张组(1.54%)和中度紧张组(5.51%)。在352名采集血样检测ADD1基因的油田工人中,rs4961基因型在不同性别、年龄和工龄组间的分布差异有统计学意义(均P0.05)。多因素logistic回归分析显示,较高的个体应对资源(OR=0.989,95%CI:0.979~0.998)和rs4961位点TT基因型(OR=0.455,95%CI:0.244~0.846)是高血压的保护因素,rs17833172位点GG基因型(OR=3.113,95%CI:1.402~6.916)是高血压的危险因素(P0.05)。[结论]油田工人高血压是基因与职业紧张综合作用的结果,较高的个体应对资源和ADD1基因rs4961位点TT基因型可能会降低油田工人高血压发病风险,ADD1基因rs17833172位点GG基因型可能会增加油田工人高血压的发病风险。     

蒙古族高血压遗传基因多态性及其交互作用

目的 探讨蒙古族人肾素-血管紧张素（RAS）系统的血管紧张素原（AGT）、血管紧张素转换酶（ACE）和血管紧张索Ⅱ1型受体（AT1R）基因多态性及其交互作用与高血压的关系。方法 在现况研究基础上，分别选择299例高血压患者和281名血压正常者进行病例对照研究。现场进行问卷调查并采集空腹静脉血；应用片段长度多态性PCR（PCR／RFLP）和单链构像多态性PCR（PCR／SSCP）方法检测基因多态性。结果 RAS系统6个位点的基因型或等位基因在病例组和对照组中频率分布的差异均无统计学意义（P〉0．05），仅男性组ACE基因I／D多态性的2组差异有统计学意义（P〈0．05）。ID＋DD基因型患高血压的危险是Ⅱ基因型的2．20倍（1．21～4．02）。交互作用分析发现。同时携带有ACE基因ID或DD基因型和AGT基因M235TMT或TT基因型者患高血压的危险性较高。结论 ACE基因ID＋DD基因型是蒙古族男性高血压的危险因素。     

山西地区血管紧张素原基因和α-内收蛋白基因多态性与原发性高血压的相关性研究

目的调查山西地区血管紧张素原(angiotensinogen,AGT)和α-内收蛋白(alpha-aduction,ADD1)基因多态性与原发性高血压(essential hypertension,EH)的关系。方法采用病例对照研究,用诱变分离聚合酶链反应(mutagenically separated polymerase chain reactions,MS-PCR)检测山西地区EH患者299例(病例组)和血压正常者218例(对照组)的AGT基因M235T多态性和ADD1基因Gly460Trp多态性。结果病例组AGT基因的TT基因型分布与对照组差异有统计学意义(P<0.001),但病例组T等位基因频率(0.426)与对照组(0.378)相比,差异无统计学意义(P=0.121)。病例组ADD1基因型分布和等位基因频率与对照组相比,差异均无统计学意义(P分别为0.306和0.072)。TT+TT联合基因型患EH的危险度增加(MT+GG:OR=0.410,P=0.041;MT+GT:OR=0.364,P=0.020;MT+TT:OR=0.262,P=0.002)。Logistic回归分析提示,AGT基因的TT基...     

高血压家系AGT基因与细胞因子关系的研究

目的 研究原发性高血压家系血管紧张素原(AGT)基因多态性及与细胞因子(IL-1、IL-6、TNF)的关系。方法 对高血压组40例和家系对照组38例用PCR-RFLP方法分析血AGT基因型，用ELISA方法测定血IL-1、IL-6和TNF浓度。结果 发现AGT235TT型在高血压组占70％，在家系对照组占42％。血IL-1和TNF浓度在高血压组比家系对照组显升高，在AGT基因235TT型中比235TM型中显升高。结论 AGT基因M235T变异是高血压发病的重要危险因素之一，细胞因子IL-1和TNF与高血压发病和AGT基因235TT型相关，它们在高血压发病中可能起重要的AGT基因调控作用。     

Angiotensinogen gene variation and hypertension in a cohort study in Japanese.

Many recent case-control studies have suggested a significant relationship between M235T (the substitution of threonine for methionine at position 235 codon) polymorphism of the angiotensinogen (AGT) gene and hypertension. To investigate whether the M235T polymorphism of AGT gene affects the incidence of hypertension, a retrospective cohort study was performed among Japanese workers. The subjects were Japanese workers at an occupational site in Shimane Prefecture in Japan. The baseline data were set at the received regular health examination in 1992, and a retrospective cohort study was performed for analyzing the incidence of hypertension in 1998. The rates of M235M (MM), M235T (MT) and T235T (TT) genotypes were 4%, 32% and 64%, respectively. The relative risks of MT and TT against MM for the incidence of hypertension by single variance analysis were 1.47 [95% confidence interval (CI) 0.50 - 4.33] and 1.35 (95% CI 0.47 - 3.90), respectively. The relative risks of MT and TT against MM for the incidence of hypertension, adjusted for sex, age, body mass index, fasting glucose and cigarette smoking, drinking and exercise in 1992, were 1.49 (95% CI 0.49 - 4.53) and 1.25 (95% CI 0.42 3.74), respectively. The data from this study suggest that the M235T polymorphism of AGT gene has a weak role in the manifestation of hypertension. Further comprehensive studies are needed to resolve this issue.     

中国原发性高血压患者血管紧张素原M235T多态性Meta分析

目的　对血管紧张素原 (AGT)基因第二外显子M2 35T多态性与原发性高血压的关联性进行Meta分析。方法　以原发性高血压组和健康对照组基因型分布的OR值为统计量。全面检索相关文献 ,剔除不符合要求的文献 ,应用REVMAN 4 .1软件对各研究结果进行一致性检验和数据合并 ,并评估发表偏倚的影响。结果　 10篇文献无明显异质性。共包括原发性高血压组患者 85 3例 ,健康对照组 835名 ,合并TT/ (MT +MM )OR =1.76 ,95 %CI :1.4 4～ 2 .16 ,P <0 .0 0 0 0 1,T/MOR =1.5 4 ,95 %CI:1.31～ 1.81,P <0 .0 0 0 0 1。结论　中国人 (汉族为主 )AGTM2 35T多态性的T等位基因和TT基因型与原发性高血压危险性增加有关联。     

Associations between RAS Gene Polymorphisms, Environmental Factors and Hypertension in Mongolian People

Objective: To explore the association between RAS system genes (AGT, ACE and AT₁R) polymorphisms, environmental factors and hypertension in Mongolian people. Methods: On the basis of cross-sectional study, a case–control study with 299 hypertensives and 281 nomotensives was conducted, and the conditions of environmental factors were acquired by questionnaire. Serum lipid and insulin were detected by using biochemical experiments. Six single nucleotide polymorphisms of RAS system were genotyped by polymerase chain reaction/restriction fragment length polymorphism and polymerase chain reaction/single strand conformation polymorphism. Results: Overweight or obesity, high serum TG and insulin resistance were risk factors of hypertension by single factor analysis. All the RAS genotype distributions were compatible with Hardy–Weinberg expectations. There were no significant differences to be found between cases and controls for genotype frequencies or allele frequencies of the six polymorphisms of RAS system, except in men group, OR value of men carried ACE ID+DD genotype vs. men carried II genotype was 2.20 (95%CI 1.21–4.02), and OR of people who carried both ACE ID (or DD) and AGT M235T MT (or MM) vs. people with both ACE ID (or DD) and AGT M235T TT was 1.59 (95%CI 1.06–2.38). Conclusions: Overweight or obesity, dyslipidemia and insulin resistance were risk factors of hypertension in Mongolian people. ACE gene ID+DD genotype was the risk factor of hypertension in men group. People who carried both ACE ID (or DD) and AGT M235T MT (or MM) had more risk to have hypertension.     

血管紧张素原基因多态性与原发性高血压关系的研究

目的 探索血管紧张素原（ＡＧＴ）的Ｍ２３５Ｔ多态性与上海市嘉定区望新乡原发性高血压的关系。方法 以人群为基础进行高血压病例－对照研究,应用ＰＣＲ－ＲＦＬＰ技术,分析ＡＧＴ的Ｍ２３５Ｔ多态性。结果 望新乡高血压病例组中ＡＧＴ基因ＴＴ基因型频率显著高于对照组,分别为４２．８％和３３．０％。相对于ＭＭ基因型,暴露于ＴＴ基因型的ＯＲ值为３．６１。病例组中Ｔ等位基因的频率也显著高于对照组,分别为７３．８９％     

Blood pressure and interactions between the angiotensin polymorphism AGT M235T and sodium intake: a cross-sectional population study

BACKGROUND: Intervention studies have indicated an interaction between the blood pressure response to a low-sodium or a low-fat and high-fruit and -vegetable diet and the angiotensinogen gene (AGT) polymorphisms G-6A and M235T. OBJECTIVE: We investigated whether this interaction is also present in a large free-living population. DESIGN: Urinary sodium, potassium as biomarkers of intake, and blood pressure were measured in 11 384 men and women aged 45-79 y participating in the Norfolk arm of the European Prospective Investigation of Nutrition and Cancer (EPIC). The M235T polymorphism was assessed by pyrosequencing. RESULTS: Highly significant associations between sodium and blood pressure were shown for all genotypes (P < 0.001), but the regression coefficient for systolic blood pressure associated with each unit of sodium for each of the MT and TT genotypes was approximately double that for the MM homozygotes (P < 0.001 for heterogeneity between genotypes). Differences were evident at high exposures to sodium but not at low exposures. There were no significant associations between blood pressure and dietary or urinary potassium. CONCLUSIONS: This large cross-sectional study supports public health recommendations to reduce salt consumption in the population as a whole, and it confirms intervention trial data showing the greatest response to intervention in persons with the AA and TT genotype in the AGT G-6A and M235T polymorphisms. Genotype effects in populations at low exposure to sodium are not likely to be seen.     

Adipose angiotensinogen secretion, blood pressure, and AGT M235T polymorphism in obese patients

OBJECTIVE: To investigate AGT secretion in cultured adipocytes from obese patients and its relationship with obesity-related phenotypes, blood pressure, and the M235T polymorphism in the AGT gene. RESEARCH METHODS AND PROCEDURES: Measurements, including anthropometry, body composition (DXA), and blood pressure, were performed in 61 overweight or obese women (BMI: 28 to 68 kg/m(2)). A subcutaneous abdominal adipose tissue biopsy was used for adipocyte size determination and quantification of AGT secretion in the medium of cultured adipocytes. AGT M235T genotype was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Adipose secretion of the AGT protein (range, 140 to 2575 ng/10(6) cells/24 h) was not significantly correlated with BMI, body fat, or blood pressure and did not vary according to the M235T polymorphism in the AGT gene. However, the AGT M235T polymorphism was associated with adipocyte size (111.6 +/- 2.8, 108.8 +/- 1.9, 118.2 +/- 2.6 micro m in MM, MT, and TT genotypes, respectively; p < 0.01) after adjustment for age and fat mass. An association between the AGT M235T polymorphism and adipocyte size (p < 0.02 adjusted for sex, age, and BMI) was found in another independent sample of 106 obese subjects (sex ratio, M/F 16/90; BMI, 29 to 70 kg/m(2)). DISCUSSION: In cultured adipocytes from obese subjects, AGT secretion was not associated with body fat phenotypes, blood pressure, or fat cell size. However, results from two independent studies suggest an association between the AGT M235T polymorphism and adipocyte size.     

Blood pressure and the T174M and M235T polymorphisms of the angiotensinogen gene.

PURPOSE: The angiotensinogen gene (AGT), which encodes the precursor of the vasoactive hormone angiotensin II, has been reported to be associated with hypertension in Caucasian and Japanese populations. We examined the relationship between two common molecular variants of AGT, T174M and M235T and blood pressure in two cohorts from the Anqing region of China. Cohort I (N = 794) consisted of families ascertained by either hypertensive or hypotensive siblings; and Cohort II (N = 761) represented a collection of randomly selected families. METHODS: Blood pressure was measured according to standard protocols, and information on age, sex, body mass index, alcohol consumption, and cigarette smoking was collected by trained interviewers using standardized questionnaires. The association of AGT genotypes and blood pressure was examined in multivariate linear regression models, with adjustment for potential intrafamilial correlations. The respective T and M allele frequencies for T174M were 0.93 and 0.07, and 0.80 and 0.20 for M235T among the parents for randomly selected families. All the analyses were conducted after exclusion of individuals currently under antihypertensive medication. RESULTS: In the pooled analysis of the two cohorts, neither the T174M nor the M235T polymorphism was significantly associated with variations of blood pressure assuming a recessive (T174M: p = 0.73 and 0.61; M235T: p = 0.99 and 0.24; for SBP and DBP), dominant (T174M: p = 0.54 and 0.72; M235T: p = 0.79 and 0.12; for SBP and DBP), or additive (T174M: p = 0.52 and 0.67, M235T: p = 0.91 and 0.11; for SBP and DBP) model. Likewise, no statistically significant association was detected when the two cohorts were analyzed separately. The logistic regression analysis of hypertension also failed to reveal any association with these markers. CONCLUSIONS: In summary, our analyses suggest that the molecular variants of AGT may not be associated with variations of blood pressure in this rural Chinese population.     

Body fat, resting and exercise blood pressure and the angiotensinogen M235T polymorphism: the heritage family study.

OBJECTIVE: The association of resting and exercise blood pressure (BP) and fat mass with the angiotensinogen (AGT) M235T polymorphism was investigated in 522 sedentary Caucasian subjects from 99 families. RESEARCH METHODS AND PROCEDURES: Resting BP was measured on two separate days, three times each day, and the mean of six valid measurements was used. Exercise BP was measured during a cycle ergometer test at a constant power output (50 W). Body composition was derived from under-water weighing and the AGT M235T polymorphism was typed with a polymerase chain reaction-based method. RESULTS: Neither resting nor exercise BP was associated with the AGT genotypes. In mothers, the homozygotes for the T allele showed 8.8 kg and 7.1 kg greater (p=0.017) age-adjusted body fat mass (FM) than the MM homozygotes and heterozygotes, respectively. Sixty-nine percent of all TT homozygotes were found in the highest FM tertile, whereas only 16% of the MM homozygotes fell in the same tertile (p = 0.008). Moreover, a significant interaction was seen between FM and T-allele carrier status in women with regard to resting diastolic BP (p = 0.002). Among women with a FM> or =24 kg, carriers of the T allele showed a 6.3 mmHg higher diastolic blood pressure (DBP) than non-carriers whereas no difference was found in women with a FM less than 24 kg. A similar trend toward an interaction term was evident with resting systolic blood pressure (p = 0.011) and exercise DBP (p = 0.012). Body fat was not associated with the AGT polymorphism in fathers or in offspring. DISCUSSION: These data suggest that the AGT M235T polymorphism is associated with body fatness in women, and that the relationship between DBP and AGT M235T polymorphism is dependent on FM in middle-aged sedentary normotensive women.