Molecular biology reports
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Molecular biology reports · Mar 2013
Meta AnalysisAssociation between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis.
The aim of this study was to determine whether the three functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518), -137 G/C (rs187238), and -1297 C/T (rs360719) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. Meta-analysis was conducted on the associations between these IL-18 polymorphisms and SLE using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 11 comparisons (nine studies) involving 8,453 subjects (2,928 SLE patients and 5,525 controls) were included in the meta-analysis. ⋯ Meta-analysis of the IL-18 -137 G/C polymorphism showed no association between SLE and the IL-18 -137 G allele in all study subjects (OR = 0.916, 95 % CI = 0.836-1.003, p = 0.057), but stratification by ethnicity indicated a significant association between this allele and SLE in Asians (OR = 0.792, 95 % CI = 0.629-0.997, p = 0.047), but not in Europeans (OR = 0.930, 95 % CI = 0.839-1.032, p = 0.171). Furthermore, meta-analysis showed that the IL-18 -1297 C allele was significantly associated with SLE in all study subjects and in Europeans (OR = 1.240, 95 % CI = 1.052-1.482, p = 0.010 and OR = 1.303, 95 % CI = 1.050-1.617, p = 0.016). This meta-analysis shows that the IL-18 -607 C/A and -1297 C/T polymorphism are associated with the development of SLE in Europeans, and the IL-18 -137 G/C polymorphism is associated with SLE in Asians.
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Molecular biology reports · Mar 2013
Meta AnalysisThe association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18,628 individuals.
Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. ⋯ Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.
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Molecular biology reports · Mar 2013
Meta AnalysisPathway analysis of genome-wide association studies for Parkinson's disease.
The study was done to identify the candidate causal single nucleotide polymorphisms (SNPs) and candidate causal mechanisms that contribute to Parkinson's disease (PD) susceptibility and to generate a SNP to ene to pathway hypothesis using an analytical pathway-based approach. We used a PD genome-wide association study (GWAS) meta-analysis data of the genotypes of 2,525,705 SNPs in 4,238 PD cases and 4,239 controls. Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied to the PD GWAS dataset. ⋯ The second stage involved the annotation of biological mechanisms for the pre-selected candidate causal SNPs using improved-gene set enrichment analysis. ICSNPathway analysis identified three candidate SNPs, two genes, twenty-one pathways, and three hypothetical biological mechanisms: (1) rs17651549 to microtubule-associated protein tau (MAPT) to protein domain specific binding (nominal p < 0.001, false discovery rate (FDR) < 0.001), neurogenesis (nominal p < 0.001, FDR < 0.001), regulation of neurogenesis (nominal p < 0.001, FDR = 0.001), positive regulation of axonogenesis (nominal p < 0.001, FDR = 0.001), regulation of protein polymerization (nominal p < 0.001, FDR = 0.004), negative regulation of organelle organization (nominal p < 0.001, FDR = 0.004), hsa01510 (nominal p < 0.001, FDR = 0.005), neuron differentiation (nominal p < 0.001, FDR = 0.009), and axonogenesis (nominal p < 0.001, FDR = 0.009); (2) rs10445337 to MAPT to protein domain specific binding (nominal p < 0.001, FDR < 0.001), neurogenesis (nominal p < 0.001, FDR < 0.001), regulation of neurogenesis (nominal p < 0.001, FDR = 0.001), and positive regulation of axonogenesis (nominal p < 0.001, FDR = 0.001); (3) rs9938550 to HSD3B7 to hsa00363 (nominal p < 0.001, FDR = 0.004), bile acid metabolic process (nominal p = 0.005, FDR = 0.019), and steroid metabolic process (nominal p = 0.010, FDR = 0.039). By applying the ICSNPathway analysis to PD GWAS meta-analysis data, three candidate SNPs, two genes (MAPT and HSD3B7), and 21 pathways involving protein domain specific binding and neurogenesis were identified, which may contribute to PD susceptibility.
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Molecular biology reports · Feb 2013
Meta AnalysisThe l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis.
The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. ⋯ Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002-1.138, P (heterogeneity) = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057-1.517, P (heterogeneity) = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961-1.146, P (heterogeneity) = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894-0.971, P (heterogeneity) = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08-5.43, P (heterogeneity) = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.
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Molecular biology reports · Dec 2012
Meta AnalysisAssociations between the FAS -670 A/G and -1,377 G/A polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis.
The aim of this study was to explore whether FAS -670 A/G and -1,377 G/A polymorphisms confer susceptibility to autoimmune rheumatic diseases. A meta-analysis was conducted on the associations between the FAS -670 A/G and -1,377 G/A polymorphisms and autoimmune rheumatic diseases using allele contrast, a recessive model, a dominant model, and an additive model. Thirteen articles with 21 comparison studies (16 on FAS -670 A/G and 5 on -1,377 G/A polymorphisms) including systemic lupus erythematosus (SLE), four systemic sclerosis, four Sjogren's syndrome, three rheumatoid arthritis (RA), one juvenile idiopathic arthritis, and one spondyloarthropathy were available for the meta-analysis. ⋯ Meta-analysis of the FAS -1,377 G/A polymorphism stratified by disease showed an association between the FAS -1,377 A allele and SLE (OR = 0.783, 95 % CI = 0.613-0.997, p = 0.047). Meta-analyses using the dominant model also showed a significant association in SLE (OR = 0.712, 95 % CI = 0.528-0.961, p = 0.027). This meta-analysis demonstrates that the FAS -670 A/G polymorphism confers susceptibility to rheumatic diseases in Asians and SLE and RA, and the FAS -1,377 G/A polymorphism is associated with SLE susceptibility.