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1.
ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.  相似文献   

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We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR = 1.48, 95% CI: 1.08–2.02, Pc = 0.03; GT: OR = 1.96, 95% CI: 1.25–3.07, Pc < 0.01), while genotype AT in this locus seemed to be protective (OR = 0.29, 95% CI: 0.02–0.72, Pc = 0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR = 2.38, 95% CI: 1.52–3.74, Pc < 0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR = 5.21, 95% CI: 2.58–10.54, Pc < 0.01); haplotype of G-T in 2677–3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR = 3.97, 95% CI: 2.31–6.85, Pc < 0.01; 2677GT/3435TT: OR = 4.55, 95% CI: 2.02–10.22, Pc < 0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677–3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.  相似文献   

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《Clinical biochemistry》2014,47(7-8):605-611
Background and objectiveA large number of studies have examined the association between the Membrane-spanning 4 domains, superfamily A, number 2 (MS4A2) gene C-109T (rs1441586) or E237G (rs569108) variants and asthma risk. However, the results are inconsistent and inconclusive. To derive a more precise estimation, a meta-analysis was performed.MethodsMeta-analyses were conducted with the data from case–control association studies (24 studies with 4496 asthmatics and 4571 controls for E237G variant and 9 studies including 2005 cases and 1868 control for C-109T polymorphisms, respectively). Random-effects model was used to calculate summary odds ratios (ORs).ResultsFor the MS4A2 gene E237G variant, no significant associations with asthma were found in overall population; we observed an elevated risk of atopic asthma among subjects with the 237G allele (OR = 1.341, 95% CI: 1.039–1.732 for G versus E and OR = 1.374, 95% CI: 1.032–1.828 for EG + GG versus EE) in the stratified meta-analysis. As for the MS4A2 gene C-109T polymorphism, no significant associations with asthma risk were observed in the total population; in subgroup analysis by ethnicity of subjects we found increased asthma risk among Asians carrying T allele (OR = 1.140, 95% CI: 1.019–1.276 for T versus C and OR = 1.359, 95% CI: 1.029–1.794 for TT versus CC).ConclusionsData indicated that the MS4A2 gene E237G variant may be a risk factor for developing atopic asthma and the promoter -109T allele is a potential risk factor of asthma in Asians.  相似文献   

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Background and objectiveNumerous studies have attempted to associate ? 58C/T polymorphism of bradykinin B2 receptor gene (BDKRB2) with hypertension, whereas results were often irreproducible. We performed a meta-analysis aiming to provide a comprehensive evaluation of this polymorphism and hypertension.MethodsCase-control reports published in English were searched totaling four studies with six populations (823 cases and 916 controls). Random-effects model was applied irrespective of between-study heterogeneity, and study quality was assessed in duplicate.ResultsCompared with ? 58C allele carriers, those with ? 58T allele had a lower yet nonsignificant risk for hypertension (OR = 0.86; 95% CI: 0.68–1.09; P = 0.21). Lack of significance persisted after combining those with genotypes ? 58TC and ? 58TT together (OR = 0.87; 95% CI: 0.67–1.09; P = 0.21) or with ? 58TC and ? 58CC together (OR = 0.75; 95% CI: 0.48–1.18; P = 0.22) in association with hypertension. Sensitivity analyses by race indicated that comparison of ? 58T versus ? 58C generated a protective effect for hypertension in Asians (OR = 0.77; 95% CI: 0.58–1.02; P = 0.07) and African-Americans (OR = 0.65; 95% CI: 0.43–0.98; P = 0.04), but a risk effect in Caucasians (OR = 1.22; 95% CI: 0.92–1.61; P = 0.17). No publication bias was observed.ConclusionsOur results suggested that ? 58T allele exhibited a protective effect on hypertension in Asians and African-Americans, yet a risk effect in Caucasians.  相似文献   

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BackgroundMatrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients.MethodsWe studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C? 1562T (rs3918242), ? 90 (CA)14–24 (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters.ResultsMMP-9 ? 90 (CA)14–24 “HH” genotype (H allele defined by number of CA repeats ≥ 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (“C, H, Q”) protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (“T, H, Q”, P = 0.0015 and P = 0.0057, respectively).ConclusionGenetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients.  相似文献   

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ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.  相似文献   

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BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.  相似文献   

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Purpose of the researchThe aim of this study was to investigate the association between risk factors and endometrial cancer in Turkish women.Methods and sampleIn a hospital-based case-control study conducted in ?stanbul, 285 patients with histologically confirmed endometrial cancer were compared with 1050 controls, admitted to the different departments of the same hospital. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from multivariate logistic regression analysis, fitted by the method of maximum likelihood.Key resultsRisk factors for endometrial cancer were found to be the state of lower education (OR = 2.53, 5% CI: 1.41–4.54), history of hypertension or diabetes (OR = 3.26, 95% CI: 2.21–4.80), (OR = 3.56, 95% CI: 2.02–6.27), lower parity (OR = 3.89, 95% CI: 2.60–5.82), early menarche age (OR = 9.43, 95% CI: 5.35–16.62) and HRT use (OR = 2.66, 5% CI: 1.40–5.06).ConclusionsIn conclusion, our results are supportive of the hypothesis that having a history of chronic disease, lower parity, early menarche and use of HRT were increased-risk factors but negative family history of cancer was decreased-risk factor for endometrial cancer.  相似文献   

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《Resuscitation》2014,85(10):1364-1369
AimWe investigated the impact of intensified postresuscitation treatment in comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology according to the initial rhythm at the emergency medical team arrival.MethodsInterventions and survival with Cerebral Performance Category (CPC) 1–2 within each group were retrospectively compared between the periods of conservative (1995–2003) and intensified (2004–2012) postresuscitation treatment.ResultsIn shockable group, therapeutic hypothermia (TH) increased from 1 to 93%, immediate invasive coronary strategy from 28 to 78%, intraaortic balloon pump from 4 to 21%, vasopressors/inotropes from 47 to 81% and antimicrobial agents from 65 to 86% during the intensified period as compared to conservative period (p < 0.001). This was associated with increased survival with CPC 1–2 from 27 to 47% (p < 0.001). After adjusting for age, sex and prehospital confounders, TH (OR = 2.12, 95% CI 1.25–3.61), percutaneous coronary intervention (OR 1.77, 95% CI 1.15–2.73) and antimicrobial agents (OR = 12.21, 95% CI 5.13–29.08) remained associated with survival with CPC 1–2. In non-shockable patients, TH also significantly increased from 1 to 74%, immediate invasive coronary strategy from 8 to 51%, intraaortic balloon pump from 2 to 9% and vasopressors/inotropes from 56 to 84% during intensified period without concomitant increase in survival with CPC 1–2 (7% vs. 9%; p = 0.27). After adjustment, only antimicrobial agents (OR = 8.43, 95% CI: 1.05–67.72) remained associated with survival with CPC 1–2.ConclusionIntensified postresuscitation treatment was associated with doubled survival in comatose survivors of OHCA with shockable rhythm. Such association could not be demonstrated in patients with non-shockable rhythm.  相似文献   

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BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.  相似文献   

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ObjectivesApolipoprotein M plays an important role in the formation of preβ-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.Design and methodsThe study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.ResultsSNP T-778C was strongly associated with T1D in both Han Chinese (p = 0.002, OR = 2.188, CI 95% = 1.338–3.581) and Swedish (p = 0.021, OR = 2.865, CI 95% = 1.128–7.278) populations. The luciferase activity of ?778C promoter was 1.41 times as high as that of ?778T promoter (9.90 ± 1.92 vs. 7.04 ± 0.76, p = 0.001).ConclusionsAllele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.  相似文献   

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BackgroundNitric oxide (NO) from the endothelium, produced by oxidation of l-arginine to l-citruline for the action at the endothelial nitric oxide synthase (eNOS) is considered an important atheroprotective factor. The 894G>T, ? 786T>C and 4a/4b polymorphic variants of the NOS3 gene have been implicated in the development of coronary artery disease (CAD). We investigated the association between occurrence of CAD documented by angiography and the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 gene in Southern Chilean individuals.MethodsA total of 112 unrelated patients with diagnosis of CAD confirmed by angiography and 112 controls were included in this study. The 894G>T and ? 786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a/4b polymorphism just for PCR.ResultsThe genotype distribution and the relative allelic frequencies for the 3 variants investigated were not significantly different between CAD and control subjects (p = NS). Moreover, the odds ratio for CAD associated with the 894T (OR = 1.22, 95% CI 0.76–1.95), ? 786C (OR = 1.16, 95% CI 0.75–1.80) and 4a (OR = 0.97, 95% CI 0.48–1.95) variants failed to reach statistical significance.ConclusionThese findings suggest that the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 were not associated with CAD in the studied subjects.  相似文献   

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BackgroundImpaired ubiquitin–proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD).MethodsWe conducted a case–control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD.ResultsNo significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls ≥ 60 years of age (P = 0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals ≥ 60 years of age (OR = 0.61; 95% CI = 0.41–0.90, P = 0.010). This is also true for T allele (OR = 0.64; 95% CI = 0.44–0.91, P = 0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR = 0.42; 95% CI = 0.22–0.81, P = 0.009) and UCHL1 C-carrying genotype (OR = 0.67; 95% CI = 0.47–0.97, P = 0.032).ConclusionsOur results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people ≥ 60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.  相似文献   

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BackgroundAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.MethodsWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.ResultsWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P = 0.025, OR = 1.47, 95% CI = 1.05–2.06; P = 0.023, OR = 1.53, 95% CI = 1.06–2.22) and adults (P = 0.018, OR = 1.10, 95% CI = 1.02–1.19; P = 0.001, OR = 1.16, 95% CI = 1.06–1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P = 0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P = 0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.ConclusionsFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.  相似文献   

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ContextMost patients admitted to acute palliative care units (APCUs) are transferred from inpatient oncology units. We hypothesized that patients admitted to APCUs from emergency centers (ECs) have symptom burdens and outcomes that differ from those of transferred inpatients.ObjectivesThe purpose of this retrospective cohort study was to compare the symptom burdens and survival rate of patients admitted to an APCU from an EC with those of inpatients transferred to the APCU.MethodsAmong the 2568 patients admitted to our APCU between September 1, 2003 and August 31, 2008, 312 (12%) were EC patients. We randomly selected 300 inpatients transferred to the APCU as controls (The outcome data were unavailable for two patients). We retrieved data on patient demographics, cancer diagnosis, Edmonton Symptom Assessment System scores, discharge outcomes, and overall survival from time of admission to the APCU.ResultsThe EC patients had higher rates of pain, fatigue, nausea, and insomnia and were less likely to be delirious. They were more than twice as likely to be discharged alive than transferred inpatients. Kaplan-Meier plot tests for product-limit survival estimate from admission to APCU for EC patients and inpatients were statistically significant (median survival 34 vs. 31 days, P < 0.0001). In multivariate analysis, EC admission (odds ratio [OR] = 1.8593, 95% confidence interval [CI] 1.1532–2.9961), dyspnea (OR = 0.8533, 95% CI 0.7892–0.9211), well-being (OR = 1.1192, 95% CI 1.0234–1.2257), and delirium (OR = 0.3942, 95% CI 0.2443–0.6351) were independently associated with being discharged alive.ConclusionThe EC patients have a higher acute symptom burden and are more likely to be discharged alive than transferred inpatients. The APCU was successful at managing symptoms and facilitating the discharge of both inpatients and EC patients to the community although the patients had severe symptoms on admission.  相似文献   

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ObjectivesMajor depressive disorder (MDD) is an increasingly recognized risk factor of coronary artery disease (CAD). The aim of this study was to assess the relationship between renin-angiotensin system (RAS) genetic polymorphisms and CAD in a sample of depressed Iranian patients.Design and methodsA total of 191 patients with a history of unipolar depression were enrolled in a case/control study. The presence of MDD was reconfirmed at study entry using DSM-IV criteria and CAD was diagnosed by coronary angiography. Genotyping of six RAS genes polymorphisms was performed by a modified PCR-RFLP method.ResultsDD genotype of ACE I/D was independently associated with the incidence of CAD in depressed patients (P = 0.011, OR = 9.41, 95% CI: 1.68–17.81). Moreover, serum creatinine (P = 0.033, OR = 11.91, 95%CI: 7.23–15.62) was an independent predictor of CAD among depressed individuals.ConclusionACE I/D polymorphism may play a major role in the development of CAD amongst Iranian depressed patients.  相似文献   

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