Association of SGK1 Polymorphisms With Susceptibility to Coronary Heart Disease in Chinese Han Patients With Comorbid Depression.
ABSTRACT: There is a strong link between heart disease and depression, both of which are closely related to lifetime stress exposure. Serum/glucocorticoid-regulated kinase 1 (SGK1) is a stress-responsive gene with a pivotal role in both the heart and brain. To determine the role of SGK1 polymorphisms (rs2758151, rs1743963, rs9493857, rs1763509, rs9376026, and rs9389154) in susceptibility to comorbid coronary heart disease (CHD) and depression, we conducted a hospital-based case-control study involving 257 CHD cases (including 69 cases with depression and 188 cases without depression) and 107 controls in a Chinese Han population. Six single-nucleotide polymorphisms (SNPs) in the SGK1 gene were successfully genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) assay. Our results showed no significant differences in SGK1 genetic polymorphisms between CHD patients and controls, whereas significant associations were observed between SGK1 SNPs (rs1743963 and rs1763509) and the development of depression in CHD patients (P = 0.018 by genotype, P = 0.032 by allele; P = 0.017 by genotype, P = 0.003 by allele, respectively). However, none of these associations remained significant after Bonferroni correction (P = 0.054 for rs1743963; P = 0.051 for rs1763509). Interestingly, both the GG genotype of SGK1 rs1743963 and AA genotype of SGK1 rs1763509 were associated with a higher risk of depression in CHD patients; for rs1763509, the Patient Health Questionnaire-9 (PHQ-9) scores in the carriers of the risk genotype for comorbid depression, AA, were significantly higher than in GG and AG carriers (P = 0.008). Notably, haplotype analysis indicated that haplotype GGA significantly increased the risk of depression in CHD patients (P = 0.011, odds ratio (OR) = 1.717, 95% confidence interval (CI) = 1.132-2.605), whereas haplotype AAG may be a protective factor for CHD patients with comorbid depression (P = 0.038, OR = 0.546, 95% CI = 0.307-0.972). It should be noted that only the significance of haplotype GGA survived after Bonferroni adjustment (P = 0.044) and that no significant differences were found for other SGK1 SNPs (rs2758151, rs9493857, rs9376026, and rs9389154) between CHD patients with and without depression. These findings, for the first time, elucidate the important role of SGK1 variants in the comorbidity of CHD and depression.
Project description:Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population.We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses.ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p?=?0.0069) even after Bonferroni correction (p?<?0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p?=?0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T???3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p?=?0.0002 and p?=?0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and larger tumor (T4). We did not find any MTHFR haplotypes associated with BC susceptibility. However, the less common haplotype MTHFR T-C was more frequent in young patients and in familial breast cancer, while MTHFR C-C haplotype was associated with sporadic BC form.Our findings are a first observation of association between ERCC2 SNPs and breast cancer in Moroccan population. The results suggested that ERCC2 and MTHFR polymorphisms may be reliable for assessing risk and prognosis of BC in Moroccan population.
Project description:BACKGROUND:To explore the relationship between CYP4F2 gene polymorphism and coronary heart disease (CHD) in a Chinese Han population. METHODS:We selected 440 CHD patients and 440 control subjects to perform a case - control study. Four SNPs (rs2108622, rs3093100, rs3093105 and rs3093135) in CYP4F2 gene were genotyped using polymerase chain reaction - restriction fragment length polymorphism (PCR - RFLP) methods. The genotype and haplotype distributions were compared between the case and the control group. RESULTS:We found both rs2108622 and rs3093105 in CYP4F2 gene were associated with the risk for CHD (P <0.01). Haplotype analysis indicated that GGGT haplotype consisted by rs2108622-rs3093100-rs3093105-rs3093135 was associated with CHD risk (OR?=?4.367, 95% CI: 2.241?~?8.510; P?<?0.001), but GGTA haplotype was associated with decreased risk for CHD (OR?=?0.450, 95% CI: 0.111?~?0.777; P <0.001). CONCLUSION:CYP4F2 gene polymorphisms were associated with the risk of CHD in Chinese population.
Project description:Our study aimed to investigate the association of ABCA1 polymorphisms with plasma lipid variability and CHD risk in the Chinese Han population.754 CHD patients and 760 controls were included in this case-control study. Three SNPs (rs363717, rs4149339, and rs4149338) in ABCA1 3'UTR and one nonsynonymous SNP (rs2230808) in ABCA1 exon 35 were selected and genotyped. The analysis of genetic data was performed using the SNPstats program and the SPSS17.0 software.Significant associations were observed between SNP rs363717 and CHD risk under different genetic models before or after Bonferroni corrections (codominant model: OR = 0.70, P = 0.003 for AG vs. AA; dominant model: OR = 0.71, P = 0.003 for GG + AG vs. AA). The nonsynonymous SNP rs2230808 was associated with higher total cholesterol levels (P = 0.047). The GCC haplotype (consisting of alleles of SNPs rs363717, rs4149339, and rs4149338) was associated with a decreased risk of CHD (OR = 0.8, P = 0.027). Three ABCA1 SNPs interacted with high triglyceride levels to increase CHD risk (P values of interactions were 0.010 for rs363717, 0.010 for rs4149339, and 0.020 for rs4149338, respectively).Our results suggest that ABCA1 polymorphisms influence plasma lipid variability and CHD risk. ABCA1 polymorphisms could also modify the effects of plasma lipids on CHD risk.
Project description:The cytotoxic T lymphocyte antigen-4 (CTLA4) gene is a key negative regulator of the T lymphocyte immune response. It has been found that CTLA4 +49A>G (rs231775), +6230G>A (rs3087243), and 11430G>A (rs11571319) polymorphisms are associated with susceptibility to many autoimmune diseases, and can down-regulate the inhibition of cellular immune response of CTLA4. Three SNPs in CTLA4 were genotyped by using the PCR and DNA sequencing methods in order to reveal the susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese. We found that the frequency of CTLA4 +49AG genotype in the pulmonary tuberculosis patients (38.42%) was significantly lower than that of the healthy controls (49.77%), (P(cor)=0.038, OR 0.653, 95% CI 0.436-0.978). But, no associations were found between the other 2 SNPs (+6230G>A, 11430G>A) and tuberculosis (P>0.05). Haplotype analysis showed that the frequency of haplotype AGG in the healthy controls group (6.9%) was significantly higher than the pulmonary tuberculosis patients group (1.4%), (global P=0.005, P(cor)=0.0002, OR 0.183, 95% CI 0.072-0.468). In addition, haplotype GGA was found to be significantly related to tuberculosis with double lung lesion rather than single lung lesion (P(cor)=0.042). This study is the first to report that genetic variants in the CTLA4 gene can be associated with pulmonary tuberculosis in Southern Han Chinese, and CTLA4 +49AG genotype as well as haplotype AGG may reduce the risk of being infected with pulmonary tuberculosis. The GGA haplotype was related to tuberculosis with double lung lesion, which provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.
Project description:Background:Coronary artery disease (CAD) and depression cause great burden to society and frequently co-occur. The exact mechanisms of this comorbidity are unclear. FK506-binding protein 51 (FKBP51) is correlated with cardiovascular disease and depression. The aim of this study was to determine the role of the seven single nucleotide polymorphisms (SNPs) of FKBP5 that code FKBP51, namely, rs1360780 (C>T), rs2817032 (T>C), rs2817035 (G>A), rs9296158 (G>A), rs9470079 (G>A), rs4713902 (T>C), and rs3800373 (C>T) in a patient's susceptibility to comorbid CAD and depression. Methods:We enrolled 271 Northern Chinese Han patients with CAD, including 123 patients with depression and 147 patients without depression. We also included 113 healthy controls that match the patients' sex and age. Genomic DNA from whole blood was extracted, and seven SNPs were assessed using MassArray method. Patient Health Questionnaire-9 was applied to access the depression. Results:The GA genotype for rs9470079 was associated with a significantly decreased risk of CAD (odds ratio = 0.506, 95% confidence interval = 0.316-0.810, P = 0.005) when the GG genotype was used as reference. A statistically significant difference was observed among females but not among males in the rs9470079 genotype and allele frequency. Patients with CAD were further divided into CAD+D and CAD-D groups according to the presence of comorbid depression and were compared with the controls. Significant differences were found regarding the genotype and allele frequency of rs2817035 and rs9470079 in CAD+H groups compared with the control subjects in all groups and the female groups (P < 0.05). Conclusions:The current study found a remarkable association between FKBP5 gene variations and the risk of comorbid CAD and depression in a north Chinese population. rs9470079 may be a potential gene locus for the incidence of comorbid CAD and depression.
Project description:To investigate the association of chemokine gene polymorphisms and Behcet's disease (BD) and Vogt Koyanagi Harada (VKH) disease in a Chinese Han population. A case-control study was performed. Three hundred and seventy-one BD patients, 371 VKH disease patients, and 605 healthy controls were recruited to determine genetic variants of 26 SNPs in 12 chemokine genes with iPLEX Gold genotyping assay and Sequenom MassARRAY or TaqMan SNP assays. In this study, Puncorr values showed a weak association of five SNPs of five genes in BD and three SNPs of three genes in VKH disease. However, after Bonferroni correction, the 26 investigated SNPs showed no significant differences in genetic variants, including genotype and allele frequencies, between BD or VKH disease patients and healthy individuals. Haplotype analysis for the chemokine genes showed a significant association with the TC haplotype of CXCL12 in VKH. Stratified gender analysis and genotype-phenotype analysis were conducted to analyze the association of the 26 SNPs of 12 chemokine genes with BD and VKH disease. However, no significant association was observed after Bonferroni correction. This study showed no association of 26 SNPs in 12 chemokine genes with both BD and VKH disease in a Chinese Han population.
Project description:Diabetes and coronary heart disease (CHD) are two of the most prevalent medical illnesses in the US population and comorbid depression occurs in up to 20% of these patients. Guidelines for management of diabetes and CHD overlap for healthy lifestyle and disease-control recommendations. However, the majority of patients with these medical illnesses have been shown to have inadequate control of key risk factors such as blood pressure, LDL cholesterol, or blood sugar. Comorbid depression has been shown to adversely affect self-care of diabetes and CHD, and is associated with an increased risk of complications and mortality. Interventions that have improved quality and outcomes of depression care alone in patients with diabetes and CHD have not demonstrated benefits in self-care, improved disease control or morbidity and mortality. This paper describes the design and development of a new biopsychosocial intervention (TEAMcare) aimed at improving both medical disease control and depression in patients with poor control of diabetes and/or CHD who met the criteria for comorbid depression. A team approach is used with a nurse interventionist who receives weekly psychiatric and primary care physician caseload supervision in order to enhance treatment by the primary care physician. This intervention is being tested in an NIMH-funded randomized controlled trial in a large integrated health plan.
Project description:The Apelin (APLN)/apelin receptor (APLNR) signaling pathway is a newly identified regulator in various cardiovascular diseases, which is considered as a candidate pathway for the occurrence of coronary heart disease (CHD), depression, and anxiety. The goal of this study was to investigate the association between APLN/APLNR gene polymorphisms and the risk of depression and anxiety in CHD patients. To this end, a case-control study involving 269 CHD patients and 184 healthy control individuals was conducted. The 269 patients with CHD including 122 patients with and 147 patients without depression, and 56 patients with and 213 patients without anxiety Four single nucleotide polymorphisms were selected and successfully genotyped using Sanger sequencing. The APLN rs2235310T allele and APLNR rs9943582C allele were found to be associated with an increased risk of CHD after multiple test correction (P-adjust < 0.05). The patients with CHD who carried the rs9943582C allele had a higher risk of depression, after adjusting for alcohol drinking habits, insomnia, hypertension, and stroke history, with the Bonferroni correction (P-adjust = 0.018). The APLNR rs2282623 T allele was associated with an increased risk of anxiety in CHD patients after adjusting for related disease complications, with the Bonferroni correction (P-adjust = 0.022). We reported for the first time that the APLN rs2235310 and APLNR rs2282623 polymorphisms are associated with the risks of psychiatric disorders in CHD patients and may serve as novel biomarkers for therapy.
Project description:BACKGROUND:This study explores the associations between PIK3CG single nucleotide polymorphisms (SNPs, rs1129293 and rs17398575) and patient responsiveness to clopidogrel to evaluate the risks of ischemia in patients with coronary heart disease (CHD). METHODS:The study consisted of 513 CHD patients who received clopidogrel as part of antiplatelet therapy, after percutaneous coronary intervention. According to the patient responsiveness to clopidogrel, the subjects were assigned to either clopidogrel-resistant (CR) or clopidogrel-sensitive (CS) groups. CR group was determined by patients' platelet aggregation rate of ?70% and poor responsiveness to clopidogrel, and CS group by patients' platelet aggregation rates of <70% and good responsiveness to clopidogrel. Polymerase chain reaction using TaqMan probe was employed to detect PIK3CG polymorphism. Haplotype and linkage disequilibrium analyses were performed. Prognosis analysis was performed using the Kaplan-Meier curve. RESULTS:Significant difference was found in genotype and rs1129293 and rs17398575 allele frequency between the CR and CS groups. Haplotype analysis indicated that the frequency of TG allele was higher in the CR group compared with the CS group, and the frequency of CA allele was lower in the CR group compared with the CS group. Patients with rs1129293 CT + TT genotype and T allele, rs1129293 AG + GG genotype and G allele exhibited an increased CR risk. Logistic regression analysis determined hypertension history as an independent risk factor for CR. The Kaplan-Meier curve suggests that distribution curve of cumulative probability nonischemic events was different between patients with rs1129293 and rs17398575 alleles. Stable CHD patients with TT genotype of rs1129293 allele and GG genotype of rs17398575 allele showed poorer prognosis compared to those with other genotypes and patients with acute coronary syndromes. CONCLUSION:A positive correlation may exist between PIK3CG SNPs (rs1129293 and rs17398575) and patients with poor responsiveness to clopidogrel. These findings show that this factor may contribute to an increased risk of ischemia in patients suffering from CHD.
Project description:OBJECTIVE:Viral infections play an important role in the development of schizophrenia, inducing the faulty immunological responses and aberrant inflammation. IFN-?-inducible protein 16 (IFI16) is an immunological DNA sensor against viral infections, triggering the inflammatory responses. In this study, we investigated an association between putative promoter single nucleotide polymorphisms (SNPs) and haplotypes of IFI16 and schizophrenia. METHODS:A total of 280 schizophrenia patients and 427 control subjects were recruited in this study. We genotyped three promoter SNPs (rs1465175, rs3754464, rs1417806) using direct sequencing. Associations of SNPs and haplotypes of IFI16 with schizophrenia were analyzed. The promoter activities on the haplotypes of IFI16 were measured. RESULTS:The T allele of rs1465175 and the C allele of rs1417806 were protectively associated with schizophrenia (p=0.021 on rs1465175; p=0.016 on rs1417806), whereas the G allele of rs3754464 was associated with an increased risk of schizophrenia (p=0.019). In haplotype analysis, a significant association between the GGA haplotype and schizophrenia was shown (p=0.013). Moreover, we found that the GGA haplotype elevated the promoter activity compared to the GAA haplotype, whereas the TAC haplotype reduced that. CONCLUSION:The promoter SNPs and haplotypes of IFI16 may contribute to the susceptibility of schizophrenia, affecting the promoter activity of IFI16.