KCNE1基因G38S多态性与新疆维吾尔族射血分数减少型慢性心力衰竭的关联性

目的 研究KCNE1基因G38S多态性与新疆维吾尔族慢性心力衰竭（CHF）的关联性。 方法 采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对新疆维吾尔族200例CHF患者（病例组）和200例无CHF患者（对照组）KCNE1基因G38S（rs1805127）多态性进行分析。 结果 KCNE1基因mink G38S多态性AA、AG、GG基因型在病例组为24（12.0%）、89（44.5%）和87（43.5%）,对照组分别为37（18.5%）、91（45.5%）和72（36.0%）。等位基因A、G频率在病例组分别为137（34.2%）,263（65.8%）,对照组分别为165（41.2%）,235（58.8%）。两组之间基因型无统计学差异（χ2=4.208,P=0.122）,两组的等位基因频率有统计学意义（P<0.05）。经二分类logistic回归分析左室舒张末内径的OR值为1.473,95% CI:（1.357~1.599）,QRS时限OR值为1.028,β=0.027,95% CI:（1.009~1.047）,性别OR值为2.288,β=0.828,95% CI:（1.059~4.943）,冠心病的OR值为3.047,β=1.114 ,95% CI:（1.532~6.063）,糖尿病OR值为3.200,β=1.163,95% CI:（1.345~7.562）。基因型AG的OR值为0.489,β=-0.715,95% CI:（0.247~0.966）。 结论 ①维吾尔族CHF患者中KCNE1基因G38S携带G等位基因频率高于对照组（无CHF患者）;②左室舒张末径增加、QRS波时限延长、男性、冠心病、糖尿病均是CHF的危险因素,携带AG基因型的维吾尔族人群发生CHF的风险小,基因型AG可能为CHF的保护因素。     

Meta-analysis of the association of 4 angiotensinogen polymorphisms with essential hypertension: a role beyond M235T?

Angiotensinogen (AGT) gene polymorphisms have been linked to increased risk of hypertension, but the data remain controversial. In this study we review the most commonly investigated polymorphisms at the AGT locus (other than M235T) and provide summary estimates regarding their association with essential hypertension, while addressing heterogeneity, as well as publication biases. Data on 26 818 subjects from 46 studies for the 4 most-studied AGT variants (T174M in exon 2 and 3 promoter variants: A-6G, A-20C, and G-217A) were meta-analyzed. Statistically significant associations with hypertension were identified for the T174M (odds ratio [OR]: 1.19; 95% CI: 1.07 to 1.33; P=0.002) and G-217A (OR: 1.37; 95% CI: 1.17 to 1.59; P=0.00006) polymorphisms. A dual but consistent effect was observed for the -20C allele, which was associated with a decreased risk of hypertension in populations of mixed and European ancestries (OR: 0.64; 95% CI: 0.44 to 0.92; P=0.02 and OR: 0.77; 95% CI: 0.65 to 0.91; P=0.003, respectively), but with a 24% increase in the odds of hypertension in Asian subjects (OR: 1.24; 95% CI: 1.04 to 1.48; P=0.02). No association of the A-6G variant with hypertension was detected. Current studies support the notion that single variants at the AGT might modulate the risk of hypertension but indicate caution in interpreting these results because of the putative presence of publication bias and gene-environment interactions.     

Interaction between gene polymorphisms of renin-angiotensin system and metabolic risk factors in premature myocardial infarction

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The authors investigated the association of genetic variability in the renin-angiotensin system (RAS) with premature MI and interactive effects between gene polymorphisms and metabolic risk factors on MI risk. Their study compared 142 patients with MI younger than 55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD (deletion/deletion) genotype conferred a twofold independent risk for MI (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA genotype were not independent risk factors for MI. An interactive effect on MI risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI= 1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1-7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD genotype is an independent risk factor for MI in patients younger than 55 years. Additionally, the authors provide evidence of an interactive effect on MI risk between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype and metabolic risk factors.     

血管紧张素原基因M235T多态性与老年脑梗死的相关性研究

目的　探讨血管紧张素原 (angiotensinogen ,AGT)基因M2 35T分子变异与脑梗死 (cerebralinfarction ,CI)之间的关系。方法　采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFLP)法对 75例CI、48例健康对照进行了AGT基因M2 35T多态性检测。结果　CI组AGT基因T2 35等位基因频率为 0 .78,2 35TT基因型频率为 0 .6 4,与对照组(分别为 0 .6 0 4和 0 .375 )比较差异具有显著性 (χ2 =8.82 ,P=0 .0 0 3;χ2 =8.2 7,P =0 .0 0 4)。校正了CI的几种危险因素 (血总胆固醇、血糖及年龄 )后 ,2 35TT基因型仍可使CI发生的危险性增加 (分别为OR =3.2 89,P =0 .0 36 ;OR =2 .49,P =0 .0 2 3)。结论　AGT基因 2 35TT型可能是脑梗死发病的独立危险因素。     

Abdominal obesity is an independent risk factor for chronic heart failure in older people

OBJECTIVES: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women. DESIGN: Prospective, longitudinal cohort: The Health, Aging and Body Composition study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas. PARTICIPANTS: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79. MEASUREMENTS: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF. RESULTS: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase). CONCLUSION: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.     

Angiotensinogen Met235Thr polymorphism, angiotensin-converting enzyme inhibitor therapy, and the risk of nonfatal stroke or myocardial infarction in hypertensive patients

The ThrThr genotype of the angiotensinogen (AGT) Met235Thr polymorphism has been associated with elevated AGT levels, hypertension, increased heart disease risk, and improved blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitors. We hypothesized that risk of stroke or myocardial infarction (MI) associated with ACE inhibitor use varies by AGT genotype, with a larger protective effect of ACE inhibitors in individuals with the ThrThr genotype than individuals who are carriers of the Met allele. METHODS: We conducted a population-based case-control study. Participants were health maintenance organization members aged 30 to 79 years with treated hypertension. Those who survived incident stroke (n = 116) or MI (n = 208) during the study period were designated as cases. Control subjects (n = 717) were randomly sampled and frequency-matched to MI cases on age, sex, and calendar year. Health history, medication use, and AGT genotype were assessed. RESULTS: ThrThr genotype was present in 21% of stroke cases, 26% of MI cases, and 19% of control subjects. Compared with nonuse, ACE inhibitor use was associated with lower stroke risk among Thr homozygotes (odds ratio [OR] = 0.37, 95% CI = 0.14 to 0.99) than among Met carriers (OR = 1.4, 95% CI = 0.88 to 2.4; P for interaction =.02). Compared with nonuse, ACE inhibitor use was associated with similar MI risk among Thr homozygotes (OR = 0.90, 95% CI = 0.62 to 1.3) and among Met carriers (OR = 1.2, 95% CI = 0.60 to 2.5; P for interaction = 0.5). CONCLUSIONS: In this hypertensive population, the association of ACE inhibitor use with risk of nonfatal stroke varied by genotype. The protective association between ACE inhibitor use and nonfatal stroke risk among individuals with ThrThr genotype was not observed for nonfatal MI.     

The involvement of the renin-angiotensin system gene polymorphisms in coronary heart disease

INTRODUCTION AND OBJECTIVES: Previous studies angiotensin-converting enzyme gene insertion/deletion polymorphism ACE (I/D), angiotensinogen gene polymorphism, and angiotensin II AT1 receptor polymorphism in relation to coronary heart disease controversial results. This study was designed to analyze the association between these gene polymorphisms and the first coronary event in individuals residing on Grand Canary Island, Spain. PATIENTS AND METHOD: Case-control study. Case subjects (n = 304) were recruited at the first coronary event; age-matched controls (n = 315) were randomly selected from the Grand Canary population. Participants were examined for the usual risk factors. Blood samples were obtained for biochemical analyses and DNA extraction. Genotyping was performed by PCR and restriction analysis. RESULTS: Neither ACE (I/D) nor AT1 receptor polymorphism was associated with coronary heart disease, whereas the frequency distribution of AGT M235T genotypes among patients and control subjects (TT: 29% and 19%; MT: 48% and 50%; MM: 22% and 31%, respectively) was statistically different (p = 0.003). Multiple logistic regression analysis identified the TT genotype of the angiotensinogen gene (OR = 1.9; 95% CI 1.1-3.4), diabetes (OR = 4.4; 95% CI 2.0-9.4) and hypertension (OR = 2.1; 95% CI 1.3-3.3) as risk factors predicting the coronary event. CONCLUSIONS: Our results provide no evidence of an association between ACE (I/D) or AT1 receptor polymorphism and coronary heart disease. However, homozygosity for the T allele of the angiotensinogen gene, diabetes and hypertension independently place individuals at higher risk of experiencing a coronary event on Grand Canary Island.     

Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population

Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II–IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) −2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5′-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56−2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36−10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69−3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20−3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08−55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.     

Association between angiotensinogen gene M235T polymorphism and mitral valve prolapse syndrome in Taiwan Chinese

BACKGROUND AND AIM OF THE STUDY: It has been reported that patients with mitral valve prolapse syndrome (MVPS) also have a disorder in autonomic or neuroendocrine function which can cause many related symptoms. Although a potential role of the reninangiotensin system in the pathogenesis of MVPS has been addressed, the role of the angiotensinogen (AGT) genetic variant in MVPS has not been studied. Thus, a case-controlled study was performed to investigate the possible relationship between AGT gene polymorphisms and MVPS. METHODS: A total of 100 patients with MVP diagnosed by echocardiography and 100 age- and sex-matched normal control subjects was studied. AGT gene M235T and T174M polymorphisms were identified by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in the distribution of AGT gene M235T genotypes (p <0.001) and allelic frequencies (p <0.001) between MVPS cases and controls. An Odds Ratio (OR) for risk of MVPS associated with M235T TT genotype was 8.55 (95% CI 4.51-16.18). An OR for risk of MVPS associated with the T allele at the M235T locus of the AGT gene was 3.27 (95% CI 2.05-5.22). The T174M polymorphism of AGT gene showed no association with MVPS (p = 0.94). CONCLUSION: These findings suggest that the M235T polymorphism of the AGT gene is associated with MVPS in the Chinese population of Taiwan. The association of the TT genotype with MVPS is more noteworthy than an overall increase in the frequency of the T allele at the M235T locus.     

Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms restriction enzyme detecting SNP of VDR (FokI and BsmI) with breast cancer risk in two independent case-control studies carried out in the same population. The modifying effect of family history of breast cancer on this relationship was also evaluated. The first and second studies included respectively 718 (255 cases/463 controls) and 1596 (622 cases/974 controls) women recruited in Quebec City, Canada. FokI and BsmI genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), FokI ff homozygotes had a higher breast cancer risk (study 1: odds ratio (OR)=1.22, 95% confidence interval (CI)=0.76-1.95; study 2: OR=1.44, 95% CI=1.05-1.99; and combined studies: OR=1.33, 95% CI=1.03-1.73). Significant interactions were observed between FokI and family history of breast cancer in the two studies as well as in the combined analysis (P interaction=0.031, 0.050 and 0.0059 respectively). Among women without family history, odds ratios were 1.00, 1.27 (95% CI=1.02-1.58) and 1.57 (95% CI=1.18-2.10) respectively for FF, Ff and ff carriers (P(trend)=0.0013). BsmI Bb+bb genotypes were associated with a weak non-significant increased risk in the two studies (combined OR=1.22, 95% CI=0.95-1.57) without interaction with family history. Results support the idea that vitamin D, through its signalling pathway, can affect breast cancer risk. They also suggest that variability in observed associations between VDR FokI and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer.     

An insulin-like growth factor-I gene polymorphism modifies the risk of microalbuminuria in subjects with an abnormal glucose tolerance

OBJECTIVE: Microalbuminuria (MA) is related to cardiovascular disease both in diabetic patients and non-diabetic subjects. DESIGN: We investigated whether a polymorphism near the promoter region of the IGF-I gene was related to the development of MA. METHODS: For this study, 1069 participants of the Rotterdam study were selected (440 participants with an abnormal glucose tolerance (AGT), 220 participants with type 2 diabetes and 254 subjects with pre-diabetes, and 595 subjects with a normal glucose tolerance (NGT). RESULTS: 787 subjects were carriers of the wild type IGF-I genotype (73.6%) and 282 subjects were variant carriers (26.4%) of this IGF-I gene polymorphism. Compared to subjects with NGT the risk for microalbuminuria was higher (Odds Ratio (OR): 3.1 (95% CI: 1.2-7.7); P = 0.02) in variant carriers with AGT than in carriers of the wild type of this IGF-I gene polymorphism (OR: 2.2 (95% CI: 1.2-4.0); P = 0.009). Compared with wild type carriers with AGT, the relative risk for MA was unadjusted and non-significantly increased in variant carriers with AGT (1.6; 95% CI: 0.8-2.9). However, after adjustment for possible confounding factors (age, gender, mean blood pressure, fasting insulin, fasting glucose and smoking) this risk became significant (OR: RR 2.1; 95% CI:1.1-4.4; P = 0.04). CONCLUSIONS: In subjects with AGT, a higher risk for MA was observed in variant carriers than in carriers of the wild type genotype of this IGF-I gene polymorphism. Since MA is primarily associated with cardiovascular disease in subjects with AGT, our study suggests that variant carriers have a higher risk for cardiovascular disease than carriers of the wild type when they develop an AGT.     

慢性心力衰竭患者肾功能恶化的危险因素分析

目的 研究慢性心力衰竭(心衰)患者肾功能恶化的危险因素及其对预后的影响.方法 采用病例对照研究方法,分析与肾功能恶化发生有统计学关联的独立危险因素,同时观察肾功能恶化对预后的影响.结果 住院心衰患者肾功能恶化发生率31%,入院肌酐水平及心功能分级与肾功能恶化的发生独立相关,OR值分别为2.248(95%CI1.088～4.647,P=0.029)和2.485(95%CI1.385～4.459.P＝0.002).发生肾功能恶化的患者住院期间病死率明显高于对照组(16.7%比2.1%,P=0.000),调整混杂因素后,肾功能恶化是死亡的独立危险因素,OR值3.824(95%CI2.452～5.137.P＜0.015).结论 肾功能恶化在住院心衰患者中发生率较高,与住院期间病死率明显相关.入院肌酐水平偏高及心功能差为发生肾功能恶化的独立危险因素.

Abstract：

Objective To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure ( CHF) and WRF influence on prognosis. Methods A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. Results The independent predictors of WRF were creatinine level at admission (OR 2.248,95% CI 1.088-4.647, P = 0.029) and NYHA class on admission ( OR 2.485, 95% CI 1.3854. 459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization( OR 3. 824,95% CI 2. 452-5. 637 ,P ＜0.015). Conclusions WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF.     

Effects of Interleukin-10 -1082G/A and -592C/A Gene Polymorphisms on the Risk of Human Immunodeficiency Virus-1 Infection: An Updated Meta-analysis

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).     

糖代谢异常对冠心病合并慢性心力衰竭的影响

目的探讨冠心病合并慢性心力衰竭（CHF）患者糖代谢异常的流行情况,以及糖代谢异常和CHF的严重程度的关系。方法研究对象分别来自北京、上海等7个城市,52家医院心内科,连续入选2005年6月至9月间所有符合CHF诊断标准的冠心病住院患者,共收集1009例,其中有效病例1004例。调查内容包括口服糖耐量试验、糖化血红蛋白、空腹血糖和血脂等;心功能分级使用美国纽约心脏病学会（NYHA）心功能分级。结果1004例患者中,过去确诊为糖尿病420（42％）例,新诊断为糖尿病175（17％）例,糖耐量异常208（21％）例,正常201（20％）例。心功能等级随着糖代谢异常程度的增加而增加[等级相关系数（L）=0．17,P=0．001]。多因素logistic回归分析发现,调整年龄等因素后,过去确诊为糖尿病、新诊断为糖尿病和IGT患严重CHF的OR值分别为1．7（95％CI：1．2～2．4）、1．4（95％CI：0．9～2．1）和1．2（95％CI：0．7～1．7）。结论CHF患者的糖代谢异常患病率较高。糖代谢异常和CHF的症状轻重相关,糖代谢异常者患严重CHF的危险性比血糖正常者高。     

Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND: Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION: Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.     

E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population

AIM: To test the hypothesis that E-cadherin gene (CDH1) C-160A promoter variant genotype is associated with an increased risk for developing gastric cancer. METHODS: In this population-based case-control study of gastric cancer in Jiangsu Province, China, we performed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to genotype the C-160A polymorphism of CDH1 promoter in 206 non-cardia gastric cancer patients and 261 age- and sex-matched but unrelated cancer-free controls. RESULTS: The frequencies of genotypes CC, CA and AA were 57.8%, 36.4% and 5.8% in gasfric cancer cases, respectively, and 58.2%, 34.9% and 6.9% in controls respectively. The distributions of CDH1 genotypes were not significantly different between gastric cancer cases and controls (P=0.87 for genotype frequency and P=0.92 for allele frequency). Compared with the CC genotype, the CA and AA genotypes were not associated with an increased risk for non-cardia gastric cancer (adjusted odds ratios (OR)=1.15, and 95% confidence interval (95% CI)=0.78-1.72 for CA genotype, and OR = 0.90 and 95% CI = 0.42-2.01 for AA genotype). CONCLUSION: E-cadherin gene C-160A promoter polymorphism may not play a major role in the etiology of non-cardia gastric cancer in Chinese population.     

肾素-血管紧张素系统基因多态性与冠心病合并慢性心力衰竭严重程度的关系

目的检测部分中国南方汉族人群冠心病合并慢性心力衰竭患者的ACE及AGT基因多态性分布情况,以探讨肾素-血管紧张素系统（1／AS）基因多态性对冠心病合并慢性心力衰竭严重程度的影响。方法应用聚合酶链反应及限制性片断长度多态性技术,对210例冠心病合并慢性心力衰竭患者的ACE基因插入／缺失（I/D）及AGT基因M235T多态性进行检测,采用彩色多普勒检测患者的左室舒张末内径（LVDD）及左室射血分数（LVEF）。结果不同ACE基因型患者其LVDD及LVEF均存在差异,LVDD（DD）〉LVDD（ID）〉LVDD（II）（P〈0．05）,LVEF（DD）〈IXEF（ID）〈LVEF（II）（P〈0．05）,不同AGT基因型亚组间LVDD及LVEF差别均无统计学意义（P〉0．05）。结论ACE基因I／D多态性与中国南方部分汉族人群冠心病合并慢性心力衰竭的严重程度相关,DD型ACE基因的冠心病患者发生心力衰竭后病情较其他基因型者更加严重。AGT基因M235T多态性似与冠心病合并慢性心力衰竭的严重程度无关。     

Association of -238G／A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population

AIM: To clarify whether -238G/A polymorphism of tumor necrosis factor-a (TNF-a) gene promoter region was associated with outcomes of hepatitis B virus (HBV) infection in Han population of northern China, and to analyze the geneenvironment interaction between -238G/A polymorphism and cigarette smoking or alcohol consumption. METHODS: A case-control study was conducted to analyze the association of TNF-a gene promoter polymorphism with HBV infection outcomes. A total of 207 patients with chronic hepatitis B (HB) and 148 cases of self-limited HBV infection from Ditan Hospital and Shunyi District Hospital in Beijing, respectively were recruited. History of smoking and alcohol drinking was inquired by a questionnaire. The -238G/A polymorphism of TNF-a gene promoter was genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). RESULTS: The frequencies of GG and GA genotypes were 98.07% and 1.93% in chronic HB patients and 93.24% and 6.76% in self-limited HBV infection individuals, respectively (X^2=5.30, P=-0.02). The frequency of G allele was significantly higher in patients with chronic HB that in individuals with self-limited HBV infection (99.03% vs 96.62%, X^2=5.20, P=0.02). Only modestly increased risk of onset of chronic HB was found in smokers (OR=1.40, 95% CI： 0.87-2.28, P=0.14) and drinkers (OR=-1.26, 95%CI： 0.78-2.05, P=-0.32). There was a positive interaction between genotype GG and cigarette smoking with an interaction index (Ⅱ) of 2.95, or alcohol consumption with an Ⅱ of 1.64. CONCLUSION: The -238G/A polymorphism of TNF-a gene promoter region is independently associated with different outcomes of HBV infection.     

Association between chronic heart failure and inhaled beta-2-adrenoceptor agonists

Background

Recent reports suggest an association between β-agonists and the risk of incident chronic heart failure (CHF). We sought to examine the association between inhaled β-agonists and risk of incident and nonincident heart failure.

Methods

We performed a nested case-control study within the Ambulatory Care Quality Improvement Project (ACQUIP). Case subjects were defined as having had a hospitalization with a primary discharge diagnosis of CHF. Controls were randomly selected from the ACQUIP cohort. The exposure was the number of β-agonist canisters filled in the 90 days before an index date.

Results

After adjusting for potentially confounding factors, there appeared to be no association between the use of inhaled β-agonists and the risk of heart failure (1-2 canisters per month, OR 1.3 [95% CI 0.9, 1.8], ≥3 canisters per month, 1.1 [95% CI 0.8, 1.6]). However, among the cohort that had a history of CHF, there appeared to be a dose-response association between the number of inhaled β-agonists and the risk of hospitalization for chronic heart failure (1-2 canisters per month, adjusted OR 1.8 [95% CI 1.1, 3.0], ≥3 canisters per month, adjusted OR 2.1 [95% CI 1.2, 3.8]).

Conclusion

β-Agonists did not appear to be associated with incident heart failure but were associated with risk of CHF hospitalization among those subjects with a previous CHF diagnosis. Although a causal relationship cannot be inferred from these findings, further research is warranted to determine the safety and effectiveness of inhaled β-agonists for patients with CHF.