Dataset Information

Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies.

ABSTRACT:

Background

Numerous epidemiological studies have evaluated the associations between ATP-binding cassette transporter 1 (ABCA1) R219K (rs2230806) and M883I (rs4149313) polymorphisms and atherosclerosis (AS), but results remain controversial. The purpose of the present study is to investigate whether these two polymorphisms facilitate the susceptibility to AS using a meta-analysis.

Methods

PubMed, Embase, Web of Science, Medline, Cochrane database, Clinicaltrials.gov, Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI, Google Scholar and Baidu Library were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0.

Results

Forty-seven articles involving 58 studies were included in the final meta-analysis. For the ABCA1 R219K polymorphism, 42 studies involving 12,551 AS cases and 19,548 controls were combined showing significant association between this variant and AS risk (for K allele vs. R allele: OR?=?0.77, 95% CI?=?0.71-0.84, P<0.01; for K/K vs. R/R: OR?=?0.60, 95% CI?=?0.51-0.71, P<0.01; for K/K vs. R/K+R/R: OR?=?0.69, 95% CI?=?0.60-0.80, P<0.01; for K/K+R/K vs. R/R: OR?=?0.74, 95% CI?=?0.66-0.83, P<0.01). For the ABCA1 M883I polymorphism, 16 studies involving 4,224 AS cases and 3,462 controls were combined. There was also significant association between the variant and AS risk (for I allele vs. M allele: OR?=?0.85, 95% CI?=?0.77-0.95, P<0.01).

Conclusions

The present meta-analysis suggested that the ABCA1 R219K and M883I polymorphisms were associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.

SUBMITTER: Yin YW

PROVIDER: S-EPMC3900558 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies.

Yin Yan-Wei YW Li Jing-Cheng JC Gao Dong D Chen Yan-Xiu YX Li Bing-Hu BH Wang Jing-Zhou JZ Liu Yun Y Liao Shao-Qiong SQ Zhang Ming-Jie MJ Gao Chang-Yue CY Zhang Li-Li LL

PloS one 20140123 1

<h4>Background</h4>Numerous epidemiological studies have evaluated the associations between ATP-binding cassette transporter 1 (ABCA1) R219K (rs2230806) and M883I (rs4149313) polymorphisms and atherosclerosis (AS), but results remain controversial. The purpose of the present study is to investigate whether these two polymorphisms facilitate the susceptibility to AS using a meta-analysis.<h4>Methods</h4>PubMed, Embase, Web of Science, Medline, Cochrane database, Clinicaltrials.gov, Current Contro ...[more]

PMID: 24466114

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Project description:ObjectivesCholesterol efflux capacity (CEC) is the main antiatherogenic function of high-density lipoprotein (HDL). ATP-binding-cassette A1 (ABCA1) membrane transporter initiates cholesterol export from arterial macrophages to pre-β HDL particles fostering their maturation; in turn, those accept cholesterol through ABCG1-mediated export. Impaired pre-β HDL maturation may disrupt the collaborative function of the two transporters and adversely affect atherosclerosis. Statins exert atheroprotective functions systemically and locally on plaque. We here evaluated associations between ABCA1-CEC, coronary atherosclerosis and cardiovascular risk and the influence of statins on those relationships in rheumatoid arthritis (RA).MethodsEvaluation with computed tomography angiography was undertaken in 140 patients and repeated in 99 after 6.9 ± 0.3 years. Events comprising cardiovascular death, acute coronary syndromes, stroke, claudication, revascularization and heart failure were recorded. ABCA1-CEC and ABCG1-CEC were evaluated in J774A.1 macrophages and Chinese hamster ovary (CHO) cells respectively and expressed as percentage of effluxed over total intracellular cholesterol. Covariates in all cardiovascular event risk and plaque outcome models included atherosclerotic cardiovascular disease (ASCVD) risk score and high-density lipoprotein cholesterol.ResultsABCA1-CEC negatively correlated with ABCG1-CEC (r = -0.167, p = 0.049). ABCA1-CEC associated with cardiovascular risk (adjusted hazard ratio 2.05 [95%CI 1.20-3.48] per standard deviation [SD] increment). There was an interaction of ABCA1-CEC with time-varying statin use (p = 0.038) such that current statin use inversely associated with risk only in patients with ABCA1-CEC below the upper tertile. ABCA1-CEC had no main effect on plaque or plaque progression; instead, ABCA1-CEC (per SD) associated with fewer baseline total plaques (adjusted rate ratio [aRR] 0.81, [95%CI 0.65-1.00]), noncalcified plaques (aRR 0.78 [95%CI 0.61-0.98]), and vulnerable low-attenuation plaques (aRR 0.41 [95%CI 0.23-0.74]) in statin users, and more low-attenuation plaques (aRR 1.91 [95%CI 1.18-3.08]) in nonusers (p-for-interaction = 0.018, 0.011, 0.025 and < 0.001 respectively). Moreover, ABCA1-CEC (per SD) associated with greater partially/fully-calcified plaque progression (adjusted odds ratio 3.07 [95%CI 1.20-7.86]) only in patients not exposed to statins during follow-up (p-for-interaction = 0.009).ConclusionIn patients with RA, higher ABCA1-CEC may reflect a proatherogenic state, associated with enhanced cardiovascular risk. Statin use may unmask the protective impact of ABCA1-mediated cholesterol efflux on plaque formation, progression and cardiovascular risk.

Dataset Information

Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies.

Background

Methods

Results

Conclusions

Publications

Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies.

Similar Datasets

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