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Diagnostic and clinical significance of antigen-specific pancreatic antibodies in inflammatory bowel diseases: A meta-analysis.
Gkiouras, K, Grammatikopoulou, MG, Theodoridis, X, Pagkalidou, E, Chatzikyriakou, E, Apostolidou, AG, Rigopoulou, EI, Sakkas, LI, Bogdanos, DP
World journal of gastroenterology. 2020;(2):246-265
Abstract
BACKGROUND Non-invasive criteria are needed for Crohn's disease (CD) diagnosis, with several biomarkers being tested. Results of individual diagnostic test accuracy studies assessing the diagnostic value of pancreatic autoantibodies-to-glycoprotein-2 (anti-GP2) tests for the diagnosis of CD appear promising. AIM: To systematically review and meta-analyze evidence on the diagnostic accuracy of anti-GP2 tests in patients with suspected/confirmed CD. METHODS An electronic search was conducted on PubMed, Cochrane-CENTRAL and grey literature (CRD42019125947). The structured research question in PICPTR format was "Population" including patients with symptoms akin to CD, the "Index test" being anti-GP2 testing, the "Comparator" involved standard CD diagnosis, the "Purpose of test" being diagnostic, "Target disorder" was CD, and the "Reference standard" included standard clinical, radiological, endoscopical, and histological CD diagnostic criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool and hierarchical models were employed to synthesize the data. RESULTS Out of 722 studies retrieved, 15 were meta-analyzed. Thirteen studies had industry-related conflicts-of-interest, and most included healthy donors as controls (spectrum bias). For the combination of IgA and/or IgG anti-GP2 test, the summary sensitivity was 20% (95% confidence interval: 10%-29%) at a median specificity of 97%. If the test was applied in 10000 suspected patients, 9669 would be true negatives and in 26, the diagnosis would be missed. In this hypothetical cohort, the anti-GP2 would fail to produce a diagnosis for 81.3% of the positive cases. Low summary points of sensitivity and high specificity were estimated for the IgG or IgA anti-GP2 test. Analogous results were observed when the analyses were restricted using specific cut-offs, or when ulcerative colitis patients were used as comparators. CONCLUSION Anti-GP2 tests demonstrate low sensitivity and high specificity. These results indicate that caution is required before relying on its diagnostic value. Additionally, the need for improving the methodology of diagnostic test accuracy studies is evident.
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Genetic association of CALHM1 rs2986017 polymorphism with risk of Alzheimer's disease: a meta-analysis.
Lu, Y, Liu, W, Tan, K, Peng, J, Zhu, Y, Wang, X
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2016;(4):525-32
Abstract
Recent studies investigating the association of Calcium homeostasis modulator 1 (CALHM1) p.P86L polymorphism (rs2986017) with Alzheimer's disease (AD) are controversial. Herein, we performed a meta-analysis to investigate the association between CALHM1 rs2986017 and AD risk. Literature searches of PubMed, Alzgene, and Embase were carried out up to 24 Nov 2015. The strength of the association between rs2986017 and AD was evaluated by odds ratio (OR) and 95 % confidence interval (CI). A total of 19 studies between 2008 and 2014 comprising 8777 AD cases and 8487 controls were included. Significant association of rs2986017 with AD was found in Caucasian population in allelic model (T vs. C: OR 1.13, 95 % CI 1.02-1.26, P = 0.022), and dominant model (TT + TC vs. CC: OR 1.15, 95 % CI 1.04-1.29, P = 0.018). No significant association was found in Asian population in any genetic model. Sensitivity analysis found that Dreses-Werringloer et al.'s might affect the overall result. The current meta-analysis suggested that CALHM1 rs2986017 might be associated with increased AD risk in Caucasian, but not Asian population.
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3.
Calcium homeostasis modulator 1 gene P86L polymorphism and the risk for alzheimer's disease: A meta-analysis.
Mun, MJ, Kim, JH, Choi, JY, Jang, WC
Neuroscience letters. 2016;:8-14
Abstract
OBJECTIVES Recently, many epidemiological studies have demonstrated an association between P86L polymorphism of calcium homeostasis modulator 1 (CALHM1) and risk for Alzheimer's disease (AD). However, the results of these association studies are inconsistent. In this study, we re-evaluated the relation between CALHM1 P86L polymorphism and risk for AD in a meta-analysis. METHODS This meta-analysis was performed using the PubMed, Science Direct, Scopus and Google Scholar databases up to June 2015 using the search terms "CALHM1" and "polymorphism or SNP or variant" in combination with "Alzheimer's disease". A meta-analysis with pooled odds ratios and 95% confidence intervals was carried out to assess the associations between P86L polymorphism and the risks for Alzheimer's disease under four genetic models with fixed or random effects models. RESULTS Sixteen studies (twenty-four subgroup studies involving 9795 cases and 15,335 controls) were included in our meta-analysis. Our meta-analysis results indicated that several genetic models of CALHM1 P86L polymorphism were significantly associated with increased risk for AD in overall and Caucasian populations. CONCLUSIONS In conclusion, our comprehensive meta-analysis indicated that P86L polymorphism is significantly associated with an increased risk for AD. Our data suggest that CALHM1 polymorphism may be potential biomarker in patients with AD.
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Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism.
Germain, M, Chasman, DI, de Haan, H, Tang, W, Lindström, S, Weng, LC, de Andrade, M, de Visser, MC, Wiggins, KL, Suchon, P, et al
American journal of human genetics. 2015;(4):532-42
Abstract
Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10(-16)) and 1.21 (p = 2.75 × 10(-15)), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology.
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A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior.
Anguelova, M, Benkelfat, C, Turecki, G
Molecular psychiatry. 2003;(7):646-53
Abstract
The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite conclusions are difficult to establish. A reliable method for assessing individual studies and generating combined results is provided by systematic reviews using meta-analytical techniques. In this study, we carried out a systematic review of studies investigating 5-HT receptors and the 5-HTT in suicidal behavior. Studies were identified by means of MEDLINE database searches and by scanning reference lists. More than 190 articles were reviewed and 26 met the inclusion criteria. In all, 14 studies investigated six different 5-HT receptor loci and 12 studies investigated the 5-HTT promoter 44 bp insertion/deletion polymorphism. Two specific meta-analyses were carried out, pooling studies investigating the 5-HT2A 102 T/C and the 5-HTT promoter loci that included, respectively, a total of 1599 and 2539 subjects. The combined evidence was significant for association with the 5-HTT locus (Mantel-Haenszel weighted odds ratio (M-H(w) OR)=1.17 CI : 1.04-1.32, P=0.009), but not for the 5-HT2A 102 T/C variant (M-H(w) OR)=1.09 CI : 0.93-1.27, P=0.319). The 5-HTT result was robust and remained significant following sensitivity analysis, suggesting that 5-HTT may play a role in the predisposition to suicide.