Dataset Information

Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis.

ABSTRACT: BACKGROUND COL1A2, which encodes collagen type I alpha2, has long been suggested to be a potential positional and functional candidate gene for intracranial aneurysm. We performed a meta-analysis to assess the association between COL1A2 rs42524 polymorphism and the risk of intracranial aneurysm. MATERIAL AND METHODS We conducted a systematic search for relevant literature from the following databases up to 22 July 2016: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The strength of association between gene and disease was estimated using odds ratios (ORs) with 95% confidence intervals (CIs) under 5 genetic models. RESULTS A total of 6 qualified studies were enrolled in this meta-analysis. Pooling results indicated a significant association between COL1A2 rs42524 polymorphism and intracranial aneurysm risk under 4 genetic models (C vs. G: OR=1.74, 95%CI=1.34-2.26; GC vs. GG: OR=1.81, 95%CI=1.37-2.41; CC+GC vs. GG: OR=1.74, 95%CI=1.28-2.36; CC vs. GC+GG: OR=1.76, 95%CI=1.02-3.04). This association was still robust when stratified by ethnicity, intracranial aneurysm type, or Hardy-Weinberg Equilibrium, which was stronger in Asian than in Caucasians. No publication bias was observed. CONCLUSIONS This meta-analysis suggests COL1A2 rs42524 is a significant risk factor for IA susceptibility, with an especially strong effect in Asian people. Further larger-scale epidemiological studies among different ethnicities are warranted to confirm our findings.

SUBMITTER: Gan Q

PROVIDER: S-EPMC5507803 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis.

Gan Qi Q Liu Qianqian Q Hu Xin X You Chao C

Medical science monitor : international medical journal of experimental and clinical research 20170703

BACKGROUND COL1A2, which encodes collagen type I alpha2, has long been suggested to be a potential positional and functional candidate gene for intracranial aneurysm. We performed a meta-analysis to assess the association between COL1A2 rs42524 polymorphism and the risk of intracranial aneurysm. MATERIAL AND METHODS We conducted a systematic search for relevant literature from the following databases up to 22 July 2016: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. ...[more]

PMID: 28671939

Similar Datasets

Project description:Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

Project description:Endoglin is an essential molecule during angiogenesis, vascular development, and integrity. Till now, many studies have investigated the association between endoglin polymorphisms and intracranial aneurysm (IA) risk, with the results remained inconclusive. Therefore, we performed a meta-analysis to summarize the possible association.We searched PubMed and Embase until June 2015 to identify studies addressing the association between endoglin polymorphisms and IA risk. The summary odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated to assess the strength of the association.Eleven studies with a total of 1501 cases and 2012 controls were finally included in this meta-analysis, with 10 studies investigating endoglin 6-bp insertion (6bINS) polymorphism and 4 studies investigating 1800956 polymorphism. No significant association between endoglin 6bINS polymorphism and IA risk was detected in overall estimation (I/I vs wt/I?+?wt/wt: OR?=?1.21, 95% CI?=?0.87-1.69) or in the subgroup analysis by ethnicity, control source, or ruptured status. However, we observed an association with borderline significance of 6bINS with IA occurrence (I/I vs wt/I?+?wt/wt: OR?=?1.49, 95% CI?=?0.99-2.25, P?=?0.058) in studies applying matched controls. Furthermore, we detected a significant association for 6bINS polymorphism of endoglin with increased risk of familial IA (I vs wt, OR?=?1.64, 95% CI?=?1.10-2.42) but not sporadic IA (I vs wt, OR?=?1.09, 95% CI?=?0.68-1.45). With regard to rs1800956, our pooled results indicated a significantly decreased IA risk in individuals carrying C allele (C/C vs G/C?+?G/G: OR?=?0.65; 95% CI?=?0.45-0.94).This meta-analysis provided no evidence for the association between 6bINS polymorphism with overall IA risk. However, we detected a significant association of 6bINS allele with increased risk of familial IA. Also, we found that rs1800956 was significantly related to IA occurrence. Further, well-designed studies with large sample size are warranted and updated meta-analysis is needed to verify our findings.

Dataset Information

Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis.

Publications

Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets