ABCMdb

PMID: 25527331

Yin YW, Wang Q, Sun QQ, Hu AM, Liu HL
ATP-binding cassette transporter 1 C69T and V825I polymorphisms in the development of atherosclerosis: a meta-analysis of 18,320 subjects.
Thromb Res. 2015 Jan;135(1):130-6. doi: 10.1016/j.thromres.2014.10.022. Epub 2014 Nov 4., [PubMed]

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No. Mutations Sentence Comment

1 ABCA1 p.Val825Ile This meta-analysis was performed to assess the associations of ABCA1 C69T and V825I polymorphisms with AS susceptibility. Login to comment 7 ABCA1 p.Val825Ile For the ABCA1 V825I polymorphism, eight studies involving 2026 AS cases and 8696 controls were combined. Login to comment 10 ABCA1 p.Val825Ile Furthermore, there was no significant association between the ABCA1 V825I polymorphism and AS risk. Login to comment 21 ABCA1 p.Val825Ile In 2003, Tan et al. found that the ABCA1 V825I polymorphism was associated with the susceptibility of coronary artery disease (CAD) among Malay population [3]. Login to comment 22 ABCA1 p.Val825Ile In 2004, Wang et al. also found significant association between the ABCA1 V825I polymorphism and ischemic stroke (IS) risk in kazakh ethnic [4]. Login to comment 33 ABCA1 p.Val825Ile In 2012, Qin et al. demonstrated no significant association between the ABCA1 V825I polymorphism and IS risk among Chinese [15]. Login to comment 34 ABCA1 p.Val825Ile In the same year, Xue et al. showed that the I/I genotype of the ABCA1 V825I polymorphism was a protective factor for IS among Chinese [7]. Login to comment 35 ABCA1 p.Val825Ile It is unclear yet whether there are significant associations between the ABCA1 C69T and V825I polymorphisms and AS risk. Login to comment 36 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Previously, we performed a meta-analysis to evaluate the associations between the ABCA1 R219K and I883M polymorphisms and AS risk, and demonstrated the above variants were the protective roles for AS [17]. Login to comment 37 ABCA1 p.Val825Ile Here, we focused on the associations between the ABCA1 C69T and V825I polymorphisms and AS risk. Login to comment 38 ABCA1 p.Val825Ile We therefore designed this meta-analysis synthesizing the data from single studies to evaluate the genetic risk of the C69T and V825I polymorphisms in ABCA1 gene for AS. Login to comment 46 ABCA1 p.Val825Ile Inclusion Criteria All studies that aimed to investigate the associations between the ABCA1 C69T and V825I polymorphisms and AS risk were considered. Login to comment 47 ABCA1 p.Val825Ile Any study which fulfilled the following criteria was included: (1) original (case-control or cohort studies) research evaluating the associations between the ABCA1 C69T and V825I polymorphisms and AS risk; (2) studied on human beings; (3) sufficient data to estimate an odds ratios (ORs) with their 95% confidence intervals (CIs); (4) not republished data. Login to comment 57 ABCA1 p.Val825Ile ORs with 95% CIs were used to measure the associations strength between the ABCA1 C69T and V825I polymorphisms and AS risk. Login to comment 58 ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile In the present meta-analysis, we evaluated the overall AS risk in four comparison models: allelic model (T allele vs. C allele for C69T; I allele vs. V allele for V825I), additive model (T/T vs. C/C for C69T; I/I vs. V/V for V825I), recessive model (T/T vs. C/T + C/C for C69T; I/I vs. V/I + V/V for V825I), and dominant model (T/T + C/T vs. C/C for C69T; I/I + V/I vs. V/V for V825I). Login to comment 68 ABCA1 p.Val825Ile After careful review, a total of 11 articles involving 14 studies (six studies for C69T polymorphism and eight studies for V825I polymorphism), comprising 3880 patients and 14440 controls, fulfilled the criteria for inclusion in this study [3-7,11-16]. Login to comment 83 ABCA1 p.Val825Ile For the ABCA1 V825I polymorphism, eight studies were combined. Login to comment 85 ABCA1 p.Val825Ile However, significant association was found between the ABCA1 V825I polymorphism and AS risk in the IS group (for I/I + V/I vs. V/V: OR =1.19, 95% CI =1.01-1.40, p =0.040). Login to comment 88 ABCA1 p.Val825Ile The included studies were limited to those conforming to HWE. Overall, the corresponding pooled ORs were not materially altered, either for the ABCA1 C69T polymorphism or for V825I polymorphism. Login to comment 92 ABCA1 p.Val825Ile Furthermore, the results of Egger`s regression test also revealed no publication bias, either for the ABCA1 C69T polymorphism (p =0.469 for allelic model, p =0.464 for additive model, p =0.586 for recessive model, and p =0.297 for dominant model, respectively) or for V825I polymorphism(p =0.459 for allelic model, p =0.921 for additive model, p =0.943 for recessive model, Fig. 1. Login to comment 97 ABCA1 p.Val825Ile Therefore, to clarify the earlier inconclusive results involving the associations between the ABCA1 C69T and V825I polymorphisms and AS risk, we performed the present meta-analysis. Login to comment 98 ABCA1 p.Val825Ile The present meta-analysis of 14 studies, including 3880 AS cases and 14440 controls, provided the most comprehensive analysis on the associations of the ABCA1 C69T and V825I polymorphisms with AS risk. Login to comment 102 ABCA1 p.Val825Ile For the ABCA1 V825I polymorphism, no significant association was found between this variant and AS risk. Login to comment 109 ABCA1 p.Val825Ile As for the ABCA1 V825I polymorphism, we did not find any evidence of association between this variant and AS risk in the Asians group and IS group. Login to comment 110 ABCA1 p.Val825Ile In contrast, significant association was found between the ABCA1 V825I polymorphism and AS risk in the CAD group suggesting the I allele carriers had a higher risk for developing AS (for OR = 1.19) compared to those with V allele. Login to comment 112 ABCA1 p.Val825Ile Position First author Year Country Ethnicity Disease Source of controls Sample size (case/control) Genotypes distribution (case/control) HWE Y/N(P) Score C69T C/C C/T T/T C T Wang [11] 2006 China Asian CAD PB 264/278 164/183 91/87 9/8 419/453 109/103 Y(0.540) 9 Ergen [12] 2008 Turkey Caucasian CAD PB 77/50 32/23 27/20 18/7 91/66 63/34 Y(0.442) 8 Yamada [5] 2008 Japan Asian IS PB 822/2070 445/1221 305/743 72/106 1195/3185 449/955 Y(0.607) 6 Porchay-Bald&#e9;relli [6] 2009 France Caucasian CAD HB 223/2906 91/1206 106/1331 26/369 288/3743 158/2069 Y(0.953) 6 Cheng [13] 2011 China Asian CAD HB 228/200 101/83 114/107 13/10 316/273 140/127 N(0.001) 6 Yi [14] 2011 China Asian IS PB 240/240 110/115 107/104 23/21 327/334 153/146 Y(0.713) 7 V825I V/V V/I I/I V I Tan-a [3] 2003 Singapore Asian CAD PB 294/108 92/34 142/58 60/16 326/126 262/90 Y(0.276) 7 Tan-b [3] 2003 Singapore Asian CAD PB 77/123 37/62 31/52 9/9 105/176 49/70 Y(0.671) 7 Tan-c [3] 2003 Singapore Asian CAD PB 83/109 71/97 10/12 2/0 152/206 14/12 Y(0.543) 7 Wang-a [4] 2004 China Asian IS PB 58/60 3/4 13/28 42/28 19/36 97/84 Y(0.389) 7 Wang-b [4] 2004 China Asian IS PB 58/60 7/12 32/34 19/14 46/58 70/62 Y(0.297) 7 Qin [15] 2012 China Asian IS PB 252/249 74/84 120/120 58/45 268/288 236/210 Y(0.851) 8 Xue [7] 2012 China Asian IS PB 97/129 36/33 50/65 11/31 122/131 72/127 Y(0.928) 7 V/V V/I + I/I Frikke-Schmidt [16] 2008 Denmark Caucasian CAD PB 1107/7858 962/6997 145/861 - 7 PB: population-based, HB: hospital-based. Login to comment 114 ABCA1 p.Val825Ile Table 2 Meta-analyses of ABCA1 C69T and V825I polymorphisms and risk of AS in each subgroup. Login to comment 115 ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile Position Sample size (case/control) Allelic model Additive model Recessive model Dominant model OR(95% CI) P OR(95% CI) P OR(95% CI) P OR(95%CI) P Overall analysis C69T 1854/5744 1.14[1.04,1.24] 0.005 1.39[1.12,1.73] 0.003 1.34[1.09,1.65] 0.006 1.13[1.01,1.27] 0.040 V825I 2026/8696 1.18[0.90,1.53]a 0.230 1.29[0.75,2.23]a 0.360 1.40[0.87,2.26]a 0.160 1.15[1.00,1.33] 0.060 Subgroup analysis based on ethnicity C69T (E) 300/2956 1.03[0.86,1.25] 0.740 1.05 [0.70,1.57] 0.820 1.03[0.70,1.50] 0.160 1.05[0.81,1.36] 0.710 C69T (A) 1554/2788 1.17[1.06,1.30] 0.003 1.58[1.21,2.05] b0.001 1.52[1.18,1.97] 0.001 1.15[1.01,1.31] 0.030 V825I (A) 919/838 1.18[0.90,1.53]a 0.230 1.29[0.75,2.23]a 0.360 1.40[0.87,2.26]a 0.160 1.06[0.85,1.32] 0.590 Subgroup analysis based on atherosclerotic diseases C69T (CAD) 792/3434 1.04[0.90,1.19] 0.620 1.07[0.76,1.51] 0.680 1.06[0.77,1.47] 0.720 1.04[0.87,1.25] 0.650 C69T (IS) 1062/2310 1.22[1.08,1.37] 0.001 1.68[1.26,2.24] b0.001 1.61[1.21,2.12] b0.001 1.19[1.03,1.39] 0.020 V825I (CAD) 1561/8198 1.18[0.92,1.50] 0.190 1.57[0.91,2.73] 0.110 1.61[0.97,2.67] 0.060 1.19[1.01,1.40] 0.040 V825I (IS) 465/498 1.18[0.74,1.89]a 0.490 1.13[0.46,2.81]a 0.790 1.27[0.61,2.64]a 0.520 1.04[0.78,1.40] 0.780 Sensitivity analysis C69T (BH) 1626/5544 1.16[1.05,1.27] 0.002 1.42[1.13,1.78] 0.002 1.35[1.09,1.68] 0.006 1.16[1.03,1.31] 0.020 V825I (BH) 919/838 1.18[0.90,1.53]a 0.230 1.29[0.75,2.23]a 0.360 1.40[0.87,2.26]a 0.160 1.06[0.85,1.32] 0.590 A: Asians, E: Europeans, PB: population-based, HB: hospital-based, BH: based on HWE (Studies with HWE were included), CAD: coronary artery disease, IS: ischemic stroke, a Significant heterogeneity: the random-effects model was chosen to summarize the result. Login to comment 117 ABCA1 p.Val825Ile In addition, considering the results produced from genetic association case-control studies may be spurious when the genotype distribution of controls deviates from HWE [28], we also performed sensitivity analyses by limiting studies to those conforming to HWE. Overall, the corresponding pooled ORs were not materially altered, either for the ABCA1 C69T polymorphism or for V825I polymorphism. Login to comment 119 ABCA1 p.Val825Ile Simultaneously, the results of sensitivity analyses further strengthened the overall conclusion involving the ABCA1 C69T and V825I polymorphisms and AS risk. Login to comment 122 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val771Met So far, at least seven single-nucleotide polymorphisms at the ABCA1 gene promoter have been studied to investigate the associations between these variants and the susceptibility of atherosclerotic diseases, such as R219K, M883I, C69T, V825I, R1587K, V771M and -565C/T. Login to comment 123 ABCA1 p.Arg219Lys In our previous study, we have demonstrated that the ABCA1 R219K and M883I polymorphisms are the protective factors for AS [17]. Login to comment 127 ABCA1 p.Val825Ile For the ABCA1 V825I polymorphism, significant between-study heterogeneity existed in the allelic model, additive model and recessive model. Login to comment 140 ABCA1 p.Val825Ile Fig. 3. Forest plots for the ABCA1 V825I polymorphism and AS risk. A (I allele vs. V allele); B (I/I vs. V/V). Login to comment 148 ABCA1 p.Val825Ile Funnel plots for the ABCA1 V825I polymorphism and AS risk. A (I allele vs. V allele); B (I/I vs. V/V). Login to comment 154 ABCA1 p.Val825Ile In addition, no significant association was found between the ABCA1 V825I polymorphism and AS risk. Login to comment 155 ABCA1 p.Val825Ile To the best of our knowledge, this is the first comprehensive meta-analysis to date investigating the associations between the ABCA1 C69T and V825I polymorphisms and AS risk. 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