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Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis.
Kristensen, G, Berg, KD, Toft, BG, Stroomberg, HV, Nolley, R, Brooks, JD, Brasso, K, Roder, MA
Journal of clinical pathology. 2019;(10):696-704
Abstract
AIMS: Zinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP). METHODS The study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP. RESULTS Median time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5). CONCLUSIONS Low AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.
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A systematic meta-analysis of the association of Neuregulin 1 (NRG1), D-amino acid oxidase (DAO), and DAO activator (DAOA)/G72 polymorphisms with schizophrenia.
Jagannath, V, Gerstenberg, M, Correll, CU, Walitza, S, Grünblatt, E
Journal of neural transmission (Vienna, Austria : 1996). 2018;(1):89-102
Abstract
The glutamate hypothesis of schizophrenia is related to the proposed dysregulation of D-amino acid oxidase (DAO), DAO activator (DAOA)/G72, and Neuregulin 1 (NRG1) genes. Genetic studies have shown significant associations between DAO, DAOA, NRG1 single-nucleotide polymorphisms (SNPs), and schizophrenia. The systematic literature search yielded 6, 5, and 18 new studies for DAO, DAOA, and NRG1 published after 2011 and not included in the previous SchizophreniaGene (SZGene) meta-analysis. We conducted meta-analyses of 20, 23, and 48 case-control studies, respectively, to comprehensively evaluate the association of 8 DAO, 12 DAOA, and 14 NRG1 SNPs with schizophrenia. The updated meta-analyses resulted in the following findings: the C-allele of DAO rs4623951 was associated with schizophrenia across all pooled studies [Odds ratio (OR) = 0.88, 95% confidence interval (CI) = 0.79-0.98, p = 0.02, N = 3143]; however, no new reports could be included. The G-allele of DAOA rs778293 was associated with schizophrenia in Asian patients (OR = 1.17, 95% CI = 1.08-1.27, p = 0.00008, N = 6117), and the T-allele of DAOA rs3916971 was associated with schizophrenia across all studies (OR = 0.84, 95% CI = 0.73-0.96, p = 0.01, N = 1765). Again, for both SNPs, no new eligible studies were available. After adding new reports, the T-allele of NRG1 SNP8NRG241930 (rs62510682) across all studies (OR = 0.95, 95% CI = 0.91-0.997, p = 0.04, N = 22,898) and in Caucasian samples (OR = 0.95, 95% CI = 0.90-0.99, p = 0.03, N = 16,014), and the C-allele of NRG1 rs10503929 across all studies (OR = 0.89, 95% CI = 0.81-0.97, p = 0.01, N = 6844) and in Caucasian samples (OR = 0.89, 95% CI = 0.81-0.98, p = 0.01, N = 6414) were protective against schizophrenia. Our systematic meta-analysis is the most updated one for the association of DAO, DAOA, and NRG1 SNPs with schizophrenia.
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The Role of Peroxisome Proliferator-Activated Receptors and Their Transcriptional Coactivators Gene Variations in Human Trainability: A Systematic Review.
Petr, M, Stastny, P, Zajac, A, Tufano, JJ, Maciejewska-Skrendo, A
International journal of molecular sciences. 2018;(5)
Abstract
BACKGROUND The peroxisome proliferator-activated receptors (PPARA, PPARG, PPARD) and their transcriptional coactivators' (PPARGC1A, PPARGC1B) gene polymorphisms have been associated with muscle morphology, oxygen uptake, power output and endurance performance. The purpose of this review is to determine whether the PPARs and/or their coactivators' polymorphisms can predict the training response to specific training stimuli. METHODS In accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses, a literature review has been run for a combination of PPARs and physical activity key words. RESULTS All ten of the included studies were performed using aerobic training in general, sedentary or elderly populations from 21 to 75 years of age. The non-responders for aerobic training (VO₂peak increase, slow muscle fiber increase and low-density lipoprotein decrease) are the carriers of PPARGC1A rs8192678 Ser/Ser. The negative responders for aerobic training (decrease in VO₂peak) are carriers of the PPARD rs2267668 G allele. The negative responders for aerobic training (decreased glucose tolerance and insulin response) are subjects with the PPARG rs1801282 Pro/Pro genotype. The best responders to aerobic training are PPARGC1A rs8192678 Gly/Gly, PPARD rs1053049 TT, PPARD rs2267668 AA and PPARG rs1801282 Ala carriers. CONCLUSIONS The human response for aerobic training is significantly influenced by PPARs' gene polymorphism and their coactivators, where aerobic training can negatively influence glucose metabolism and VO₂peak in some genetically-predisposed individuals.
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TRIM5α H43Y Polymorphism and Susceptibility to HIV-1 Infection: A Meta-Analysis.
Deng, J, Chen, Y, Ding, D, Lu, P, Yang, X, Song, Z, Zhu, H
AIDS research and human retroviruses. 2015;(12):1213-8
Abstract
TRIM5α is an antiviral factor that can greatly limit HIV-1 infection. Although several researchers have investigated whether TRIM5α H43Y polymorphism influences the risk of HIV-1 infection, no definite conclusion has ever been drawn. In this research, we performed a meta-analysis to generate a more robust estimate of the association between TRIM5α H43Y and susceptibility to HIV-1 infection. In total, six studies including 1,713 HIV-1 patients and 1,814 controls were included. TRIM5α H43Y polymorphisms of all individuals were genotyped. Odds ratios (ORs) with 95% confidence intervals were presented as the result of analysis. ORs for the main analysis were 0.82 (95% CI: 0.63-1.08) in the allelic comparison, 0.57 (95% CI: 0.34-0.95) in the homozygote comparison, 0.82 (95% CI: 0.57-1.16) in the dominant model, and 0.56 (95% CI: 0.33-0.93) in the recessive model. In the subgroup analysis by ethnicity, significantly decreased risks of infection were detected in the Asian population (homozygote comparison: 0.50, 95% CI: 0.28-0.89; recessive model: 0.49, 95% CI: 0.28-0.87), whereas such effects were not observed in the non-Asian population. Our meta-analysis indicates that TRIM5α H43Y polymorphism is associated with a decreased risk of HIV-1 infection in the homozygote comparison and recessive model. This polymorphism may act as a protective factor against HIV-1 infection, especially in Asians.
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Identification of Genes Expressed in Hyperpigmented Skin Using Meta-Analysis of Microarray Data Sets.
Yin, L, Coelho, SG, Valencia, JC, Ebsen, D, Mahns, A, Smuda, C, Miller, SA, Beer, JZ, Kolbe, L, Hearing, VJ
The Journal of investigative dermatology. 2015;(10):2455-2463
Abstract
More than 375 genes have been identified that are involved in regulating skin pigmentation and these act during development, survival, differentiation, and/or responses of melanocytes to the environment. Many of these genes have been cloned, and disruptions of their functions are associated with various pigmentary diseases; however, many remain to be identified. We have performed a series of microarray analyses of hyperpigmented compared with less pigmented skin to identify genes responsible for these differences. The rationale and goal for this study was to perform a meta-analysis on these microarray databases to identify genes that may be significantly involved in regulating skin phenotype either directly or indirectly that might not have been identified due to subtle differences by any of these individual studies alone. The meta-analysis demonstrates that 1,271 probes representing 921 genes are differentially expressed at significant levels in the 5 microarray data sets compared, providing new insights into the variety of genes involved in determining skin phenotype. Immunohistochemistry was used to validate two of these markers at the protein level (TRIM63 and QPCT), and we discuss the possible functions of these genes in regulating skin physiology.
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Genetic variants in the CPNE5 gene are associated with alcohol dependence and obesity in Caucasian populations.
Wang, KS, Zuo, L, Pan, Y, Xie, C, Luo, X
Journal of psychiatric research. 2015;:1-7
Abstract
Alcohol addiction may increase the risk of obesity due to shared genetic components. The Copine V (CPNE5) gene is involved in Ca(2+) binding and may play an important role in the development of the central nervous system. This study tested the genetic associations of 77 single-nucleotide polymorphisms (SNPs) within the CPNE5 gene with alcohol dependence (AD) and obesity using a Caucasian sample - The Study of Addiction - Genetics and Environment (SAGE) sample (1066 AD cases and 1278 non-AD controls, 422 obese cases and 1395 non-obese controls). The Marshfield sample (1442 obese cases and 2122 non-obese controls) was used for replication of obesity. Multiple logistic regression analysis was performed using the PLINK software. In the SAGE sample, we identified 10 SNPs associated with AD and 17 SNPs associated with obesity (p < 0.05). Interestingly, 6 SNPs (rs9986517, rs9470387, rs3213534, rs10456444, rs3752482, and rs9470386) were associated with both AD (OR = 0.77, 0.77, 0.83, 0.84, 0.79 and 1.14, respectively; p = 9.72 × 10(-5), 1.1 × 10(-4), 4.09 × 10(-3), 5.26 × 10(-3), 1.59 × 10(-2), and 3.81 × 10(-2), respectively) and obesity (OR = 0.77, 0.77, 0.78, 0.77, 0.68 and 1.18, respectively; p = 2.74 × 10(-3), 2.69 × 10(-3), 2.45 × 10(-3), 1.01 × 10(-3), 5.18 × 10(-3) and 3.85 × 10(-2), respectively). In the Marshfield sample, rs3752480 was associated with obesity (p = 0.0379). In addition, four SNPs (rs9986517, rs10456444, rs7763347 and rs4714010) showed associations with obesity in the meta-analysis using both samples (p = 0.00493, 0.0274, 0.00346, and 0.0141, respectively). These findings provide the first evidence of common genetic variants in the CPNE5 gene influencing both the AD and obesity; and will serve as a resource for replication in other populations.
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Transethnic meta-analysis suggests genetic variation in the HEME pathway influences potassium response in patients treated with hydrochlorothiazide.
Del-Aguila, JL, Cooper-DeHoff, RM, Chapman, AB, Gums, JG, Beitelshees, AL, Bailey, K, Turner, ST, Johnson, JA, Boerwinkle, E
The pharmacogenomics journal. 2015;(2):153-7
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Abstract
Hypokalemia is a recognized adverse effect of thiazide diuretic treatment. This phenomenon, which may impair insulin secretion, has been suggested to be a reason for the adverse effects on glucose metabolism associated with thiazide diuretic treatment of hypertension. However, the mechanisms underlying thiazide diuretic-induced hypokalemia are not well understood. In an effort to identify genes or genomic regions associated with potassium response to hydrochlorothiazide, without a priori knowledge of biologic effects, we performed a genome-wide association study and a multiethnic meta-analysis in 718 European- and African-American hypertensive participants from two different pharmacogenetic studies. Single-nucleotide polymorphisms rs10845697 (Bayes factor=5.560) on chromosome 12, near to the HEME binding protein 1 gene, and rs11135740 (Bayes factor=5.258) on chromosome 8, near to the Mitoferrin-1 gene, reached genome-wide association study significance (Bayes factor >5). These results, if replicated, suggest a novel mechanism involving effects of genes in the HEME pathway influencing hydrochlorothiazide-induced renal potassium loss.
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MTP -493G>T polymorphism and susceptibility to nonalcoholic fatty liver disease: a meta-analysis.
Zheng, W, Wang, L, Su, X, Hu, XF
DNA and cell biology. 2014;(6):361-9
Abstract
Microsomal transfer protein (MTP), a lipid transfer protein localized in the endoplasmic reticulum of hepatocytes and enterocytes, plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). Many existing studies have demonstrated that a common polymorphism (-493G>T, rs1800591 G>T) in the MTP gene may be implicated in the development and progression of NAFLD, but individually published results are inconclusive. This meta-analysis aimed to investigate whether MTP -493G>T polymorphism may be a potential risk factor for NAFLD. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through October 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Eleven clinical case-control studies with a total of 636 NAFLD cases and 918 healthy controls met the inclusion criteria. Our meta-analysis results revealed that MTP -493G>T polymorphism was strongly correlated with an increased risk of NAFLD. Subgroup analysis by ethnicity suggested that MTP -493G>T polymorphism might increase individuals' susceptibility to NAFLD among both Caucasian and non-Caucasian populations. No publication bias was observed in this meta-analysis. In short, the present meta-analysis indicates that MTP -493G>T polymorphisms may contribute to individuals' susceptibility to NAFLD. Thus, MTP -493G>T polymorphism may be a valuable and practical biomarker for early detection of NAFLD.
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Association of glucokinase regulatory protein polymorphism with type 2 diabetes and fasting plasma glucose: a meta-analysis.
Li, H, Xu, R, Peng, X, Wang, Y, Wang, T
Molecular biology reports. 2013;(6):3935-42
Abstract
Glucokinase regulatory protein (GCKR) which binds to glucokinase (GCK) in the nucleus and inhibits its activity in the presence of fructose-6-phosphate is critical for glucose metabolism. In the past few years, a number of case-control studies have been carried out to investigate the relationship between the GCKR polymorphism and type 2 diabetes (T2D) since it was first identified to be associated with fasting plasma glucose levels, insulin resistance through genome-wide association approach. After that, a number of studies reported that the rs780094 polymorphism in GCKR has been implicated in T2D risk. However, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 19 studies involving a total of 298,977 subjects for GCKR rs780094 to evaluate its effect on genetic susceptibility for T2D. In a combined analysis, the summary per-allele odds ratio for T2D of the rs780094 polymorphism was 1.11 (95 % CI: 1.07-1.14, P < 10(-5)). Significant results were also observed using dominant (OR = 1.18, 95 % CI: 1.05-1.34, P < 10(-5)) or recessive genetic model (OR = 1.20, 95 % CI: 1.12-1.28, P < 10(-5)). Significant results were found in Asians and Caucasians when stratified by ethnicity. Besides, the polymorphism was found to be significantly associated with increased fasting plasma glucose level. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis suggests that the rs780094 polymorphism in GCKR is associated with elevated T2D risk, but these associations vary in different ethnic populations.
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Association between three genetic variants of the Perilipin Gene (PLIN) and glucose metabolism: results from a replication study among Chinese adults and a meta-analysis.
Yu, D, Li, C, Xie, J, Xu, G, Li, Y, Liu, J, Chen, B, Pan, J, Shen, M, Yang, L, et al
Endocrine research. 2013;(4):263-79
Abstract
OBJECTIVE This study was aimed to replicate the associations between three Perilipin Gene (PLIN) variants (rs894160, rs1052700, and rs2304796) and diabetes risks and to evaluate the overall effects of these variants on diabetes risk and obesity risk. METHODS We conducted a cross-sectional study among 993 Chinese Han adults. We also made a meta-analysis to estimate associations between these variants and diabetes risk and obesity risk. RESULTS In the sample of all participants, all three single-nucleotide polymorphisms (SNPs) were not significantly associated with diabetes risks. The PLIN polymorphisms significantly interacted with central obesity in relation to diabetes risk (P for interaction = 0.036, 0.033, and 0.042 for rs1052700, rs894160, and rs2304796, respectively). In those with allele T of rs1052700 or allele A of rs894160, fasting glucose concentration and diabetes risk increased significantly with the increment of waist circumference. Only association between rs894160 and obesity risk was available for meta-analysis. The meta-analysis indicated the overall estimation of obesity risk for rs894160 was 0.97 (0.78, 1.16) among participants with allele A versus people with genotype GG and 1.46 (0.99, 1.93) among those with genotype AA versus allele G carriers. CONCLUSION Chinese adults with high waist circumference may have a high risk of diabetes, especially among those with allele T in rs1052700 or with allele A in rs894160. People with genotype AA (rs894160) may have a high risk of obesity.