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1.
The association between copper transporters and the prognosis of cancer patients undergoing chemotherapy: a meta-analysis of literatures and datasets.
Sun, S, Cai, J, Yang, Q, Zhao, S, Wang, Z
Oncotarget. 2017;(9):16036-16051
Abstract
Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effect models. Subgroup analysis and sensitivity analysis were conducted; heterogeneity and publication bias were assessed. Twelve literatures and eight datasets with 2149 patients were included. Our results suggested that high CTR1 expression was associated with favorable OS, PFS, DFS and TR in cancer patients who underwent chemotherapy with acceptable heterogeneity. The relationship of CTR1 to cancer prognosis remained significant in the subgroup of patients who underwent platinum-based chemotherapy, the patients with ovarian cancer and those with lung cancer. The significance of these relationships was not influenced by geological region of publication, data origin or detection method. However, there was no evidence for relation of CTR2, ATP7A or ATP7B to OS, PFS, DFS or TR. Test of publication bias and sensitivity analysis suggested a robustness of all the summary effect estimates. In conclusion, high CTR1 level predicts prolonged survival and enhanced response to chemotherapy in cancer patients who underwent chemotherapy and CTR1 might be a potential target to circumvent chemotherapy resistance.
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Common variants in the chromosome 2p23 region containing the SLC30A3 (ZnT3) gene are associated with schizophrenia in female but not male individuals in a large collection of European samples.
Perez-Becerril, C, Morris, AG, Mortimer, A, McKenna, PJ, de Belleroche, J
Psychiatry research. 2016;:335-340
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Abstract
Previously, we found a significant gender-specific association of schizophrenia, in a UK case/control study, with SLC30A3, a candidate that is consistently down-regulated in schizophrenia in two independent cohorts. In view of the potential significance of this finding, we extended this study to a larger cohort using GWAS data from the Psychiatric Genetic Consortium (PGC). Meta-analysis was performed for the only two SLC30A3 SNP variants (rs11126936 and rs11126929) available in most PGC cohorts. A significant association with schizophrenia was found for both variants. When meta-analysis was performed in male and female case-control subsets, an increased and gender-specific effect of allele on risk of disease was found in females for both SNPs with no significant effect in males, which was further associated with a gender-specific effect on gene expression. In conclusion, using a large European-wide sample we were able to replicate the gender-specific association previously found in a UK cohort.
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Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis.
Fan, M, Li, W, Wang, L, Gu, S, Dong, S, Chen, M, Yin, H, Zheng, J, Wu, X, Jin, J, et al
Endocrine. 2016;(2):381-94
Abstract
The solute carrier family 30 member 8 (SLC30A8) gene may be involved in the development of type 2 diabetes mellitus (T2DM) through disrupting β-cell function. The aim of this study was to assess the association between SLC30A8 rs13266634 polymorphism and susceptibility to T2DM. We searched all reports regarding the association between SLC30A8 rs13266634 polymorphism and T2DM risk through Pubmed, Embase, and the Cochrane Library for English language reports and Chongqing VIP database, Wanfang data, CBMDisc, and CNKI for Chinese language studies. Allelic and genotype comparisons between cases and controls were evaluated, and odds ratios with 95 % confidence intervals were used to assess the strength of their association. A random effects model was selected. Publication bias was estimated using Begg's test. Forty-six studies were included in the analysis with a total of 71,890 cases and 96,753 controls. This meta-analysis suggests that SLC30A8 (rs13266634) polymorphism was associated with T2DM risk. Although previous meta-analyses have shown that this association was only found in Asian and European groups, and not in African populations, our analysis revealed the deleterious effect of SLC30A8 rs13266634 on T2DM in an African population when stratified by ethnicity under additive model even with a small number of studies.
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Association between SLC30A8 rs13266634 Polymorphism and Type 2 Diabetes Risk: A Meta-Analysis.
Cheng, L, Zhang, D, Zhou, L, Zhao, J, Chen, B
Medical science monitor : international medical journal of experimental and clinical research. 2015;:2178-89
Abstract
BACKGROUND Accumulating but inconsistent data about the role of rs13266634 variant of SLC30A8 in type 2 diabetes have been reported, partly due to small sample sizes and non-identical ethnicity. MATERIAL AND METHODS We searched PubMed and Cochrane Library to identify eligible studies and extract data of baseline characteristics, genotype count, odds ratio (OR), and 95% confidence interval (CI). Both adjusted OR with 95% CI and genotype counts were employed to assess the association. Genotype data were further pooled to provide estimates under different genetic models and the most appropriate model was determined. Sensitivity and cumulative analysis were conducted to assure the strength of results. RESULTS Fifty-five datasets of 39 studies (including 38 of 24 with genotype count) were included. Significant associations were found in allelic contrasts using adjusted ORs and raw genotype count, respectively, overall in Asian and European populations (overall: OR=1.147/1.157, 95% CI 1.114-1.181/1.135-1.180; Asian: OR=1.186/1.165, 95% CI 1.150-1.222/1.132-1.198; European: OR=1.100/1.151, 95% CI 1.049-1.153/1.120-1.183; All p=0.00), but not in African populations (African: OR=1.255/1.111, 95% CI 0.964-1.634/0.908-1.360, p=0.091/0.305). Further analysis with genotype count under different genetic models all showed that individuals with CC genotype had 33.0% and 16.5% higher risk of type 2 diabetes than those carrying TT and CT genotypes, respectively, under the most likely codominant model. Cumulative analysis indicated gradually improved precision of estimation after studies accumulated. CONCLUSIONS Our results suggest that rs13266634 may be an important genetic factor of type 2 diabetes risk among Asian and European but not African populations.
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Association between rs13266634 C/T polymorphisms of solute carrier family 30 member 8 (SLC30A8) and type 2 diabetes, impaired glucose tolerance, type 1 diabetes--a meta-analysis.
Xu, K, Zha, M, Wu, X, Yu, Z, Yu, R, Xu, X, Chen, H, Yang, T
Diabetes research and clinical practice. 2011;(2):195-202
Abstract
AIMS: To investigate the association of solute carrier family 30 member 8 (SLC30A8) rs13266634 C/T polymorphism with type 2 diabetes (T2DM), impaired glucose tolerance (IGT), and type 1 diabetes (T1DM). METHODS We searched all the publications about the association between SLC30A8 and diabetes from PubMed, and evaluated the association between SLC30A8 rs13266634 C/T polymorphism and T2DM, IGT and T1DM, respectively, by meta-analysis of all the validated studies. Allelic and genotypic comparisons between cases and controls were evaluated. RESULTS Thirty six studies were included in the meta-analysis: 31 studies were analysed for rs13266634 C/T polymorphism with T2DM, 3 studies with IGT and 4 studies with T1DM. The pooled odds ratios (ORs) for allelic and genotypic comparisons (including additive model, co-dominant model, dominant model and recessive model) showed that rs13266634 C/T polymorphism was significantly associated with increased T2DM risk: OR=1.15, 95% confidence interval (CI)=1.13-1.17, P<0.001, P(heterogeneity)=0.041, OR=1.34, 95% CI=1.26-1.41, P<0.001, P(heterogeneity)=0.908, OR=1.20, 95% CI=1.16-1.24, P<0.001, P(heterogeneity)=0.699, and OR=1.23, 95% CI=1.17-1.30, P<0.001, P(heterogeneity)=0.801, respectively. In subgroup analyses, we found that rs13266634 C/T polymorphism was associated with T2DM risk both in Asian and European subgroup (P<0.001), but not in African (P>0.05). And the pooled odds ratio (OR) for allelic frequency comparison showed that rs13266634 C/T polymorphism was also significantly associated with IGT: OR=1.15, 95% CI=1.06-1.26, P<0.001, P(heterogeneity)=0.364. Meanwhile, our meta-analysis did not suggest that rs13266634 C/T polymorphism was associated with T1DM risk (P>0.05): OR=1.02, 95% CI=0.98-1.06, P=0.328, P(heterogeneity)=0.488 for allelic frequency comparison. CONCLUSIONS Our meta-analysis results revealed the significant association between rs13266634 C/T polymorphism and T2DM and IGT, but did not support the association between this polymorphism and T1DM.
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Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets.
Cauchi, S, Del Guerra, S, Choquet, H, D'Aleo, V, Groves, CJ, Lupi, R, McCarthy, MI, Froguel, P, Marchetti, P
Molecular genetics and metabolism. 2010;(1):77-82
Abstract
BACKGROUND The C-allele of rs13266634 located in SLC30A8 (ZNT8) has been strongly associated with decreased insulin release and with type 2 diabetes (T2D) susceptibility in some but not all studies. To shed further light on this issue, we performed a meta-analysis of the association between rs13266634 and T2D in different ethnic groups and assessed the relationships between SLC30A8 genotypes and some properties of isolated human islets. METHODS From 32 original articles, a total of 77,234 control individuals and 44,945 subjects with T2D were studied in meta-analysis. To assess the relationships between SLC30A8 genotype and islet cell phenotype, insulin secretion in response to glucose, glucose plus arginine and glucose plus glibenclamide was determined in pancreatic islets isolated from 82 multiorgan donors genotyped for the rs13266634 polymorphism. Quantitative expression of SLC30A8, Insulin and Glucagon mRNA was also measured. RESULTS Overall, each SLC30A8 risk allele was associated with a 14% increased risk for T2D (P=2.78 x 10(-34)). The population risk of T2D attributable to this polymorphism was estimated at 9.5% in Europeans and 8.1% in East Asians. Basal and stimulated insulin secretion from human islets as well as islet expressions of SLC30A8, Insulin and Glucagon were not affected by the presence of the polymorphism. However, SLC30A8 expression was positively correlated with Insulin (r=0.75, P=6.43 x 10(-6)) and Glucagon (r: 0.70, P=4.89 x 10(-5)) levels. CONCLUSIONS The SLC30A8 rs13266634 polymorphism is among the most confirmed genetic markers of T2D in Europeans and East Asians. In isolated human islets, the risk C-allele does not affect ex-vivo insulin secretion and SLC30A8 expression, which is correlated with that of insulin and glucagon.
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Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis.
Nishino, M, Ikegami, H, Fujisawa, T, Kawaguchi, Y, Kawabata, Y, Shintani, M, Ono, M, Ogihara, T
Metabolism: clinical and experimental. 2005;(5):628-33
Abstract
The association of the polymorphism of the Z-DNA-forming repeats in the promoter region of SLC11A1 (solute carrier family 11 member 1), formerly designated NRAMP1 (natural resistance associated macrophage protein 1), with type 1 diabetes was studied in a total of 244 Japanese subjects. Three alleles were detected in Japanese subjects. In diabetic patients, allele 2 was less frequent and allele 3 was more frequent, albeit not significantly, than in control subjects. Allele 2 was significantly ( P < .024) less frequent whereas allele 3 was more, albeit not significantly, frequent in the younger onset group than in the control subjects. In patients with a susceptible HLA allele, DRB1*0405 or DRB1*0901 , the frequency of allele 2 was significantly ( P < .013) lower and that of allele 3 tended to be higher than that in patients without either DRB1*0405 or DRB1*0901 . The protective effect of allele 2 against type 1 diabetes and other autoimmune diseases was confirmed by meta-analysis (summary odds ratio, 0.71, 95% confidence interval, 0.53-0.96). Because allele 2 was shown to be associated with low expression of SLC11A1 and protection against another autoimmune disease, rheumatoid arthritis, the negative association of allele 2 with autoimmune type 1 diabetes in the present study suggests that a less active immune system in subjects with allele 2 may protect individuals from autoimmune diseases.
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The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis.
Stapelbroek, JM, Bollen, CW, van Amstel, JK, van Erpecum, KJ, van Hattum, J, van den Berg, LH, Klomp, LW, Houwen, RH
Journal of hepatology. 2004;(5):758-63
Abstract
BACKGROUND AND AIMS Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype. METHODS Genotyping results in 70 Dutch patients were related to clinical presentation. Subsequently a meta-analysis for genotype-phenotype correlation was performed on all patients available from literature, combined with the current Dutch group, a total of 577 patients. RESULTS The Dutch patients homozygous or heterozygous for the H1069Q mutation presented more frequently with neurologic disease (63% and 43% vs. 15%), and at a later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q mutation. In the meta-analysis the odds-ratio for neurologic presentation in homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95% CI 2.01-6.09) and 2.13 (95% CI 1.18-3.83), respectively. Age at presentation was 21.1, 19.2 and 16.5 years, respectively, corresponding to a weighted mean difference (WMD) of 4.41 (95% CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients and 6.68 (95% CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients. CONCLUSIONS Our results indicate that the H1069Q mutation is associated with a late and neurologic presentation.