ABCMdb

PMID: 24466114

Yin YW, Li JC, Gao D, Chen YX, Li BH, Wang JZ, Liu Y, Liao SQ, Zhang MJ, Gao CY, Zhang LL
Influence of ATP-binding cassette transporter 1 R219K and M883I polymorphisms on development of atherosclerosis: a meta-analysis of 58 studies.
PLoS One. 2014 Jan 23;9(1):e86480. doi: 10.1371/journal.pone.0086480. eCollection 2014., [PubMed]

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1 ABCA1 p.Arg219Lys , Dong Gao1 , Yan-Xiu Chen2 , Bing-Hu Li1 , Jing-Zhou Wang1 , Yun Liu1 , Shao-Qiong Liao1 , Ming-Jie Zhang1 , Chang-Yue Gao1 , Li-Li Zhang1 * 1 Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Yuzhong District, Chongqing, PR China, 2 Department of Neurology, The brain hospital of Liaocheng Hospital, Liaocheng, Shandong, PR China 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. Login to comment 6 ABCA1 p.Arg219Lys 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). Login to comment 9 ABCA1 p.Arg219Lys Conclusions: The present meta-analysis suggested that the ABCA1 R219K and M883I polymorphisms were associated with the susceptibility to AS. Login to comment 11 ABCA1 p.Arg219Lys Citation: Yin Y-W, Li J-C, Gao D, Chen Y-X, Li B-H, et al. (2014) Influence of ATP-Binding Cassette Transporter 1 R219K and M883I Polymorphisms on Development of Atherosclerosis: A Meta-Analysis of 58 Studies. Login to comment 28 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val771Met Recently, a number of molecular epidemiological studies have been done to evaluate the associations between the ABCA1 gene polymorphisms (such as R219K, M883I, C69T, V825I, R1587K, V771M and 2565C/T) and the risk of atherosclerotic diseases [248]. Login to comment 30 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys In 2011, Ma et al. performed a meta-analysis to evaluate the association between the ABCA1 R219K polymorphism and coronary artery disease (CAD), and demonstrated that the ABCA1 R219K polymorphism was a protective role for CAD both in Asians and Caucasians [53]. Login to comment 32 ABCA1 p.Arg219Lys However, they just found the ABCA1 R219K polymorphism was a protective factor in Asians, but not in Caucasians. Login to comment 33 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Considering the above two meta-analyses only focused on the association of ABCA1 R219K polymorphism with the single atherosclerotic disease, we therefore performed this meta-analysis of all the studies available now to derive a more precise estimation of the associations between the ABCA1 R219K and M883I polymorphisms and overall AS risk. Login to comment 41 ABCA1 p.Arg219Lys Inclusion and Exclusion Criteria To be included in the present meta-analysis, the studies had to comply with the following major criteria: (1) case-control or cohort studies evaluating the associations between the ABCA1 R219K and M883I polymorphisms and AS risk; (2) published studies with full text articles; (3) Diagnosises of atherosclerotic diseases were made according to the internationally recognized diagnostic criterion. Login to comment 54 ABCA1 p.Arg219Lys The strength of associations between the ABCA1 R219K and M883I polymorphisms and AS risk were assessed by ORs with 95% CIs. Login to comment 55 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys The pooled ORs were performed for allelic model (K allele vs. R allele for R219K; I allele vs. M allele for M883I), additive model (K/K vs. R/R for R219K; I/I vs. M/M for M883I), recessive model (K/K vs. R/K+R/R for R219K; I/I vs. M/I+M/M for M883I), and dominant model (K/K+R/K vs. R/R for R219K; I/I+M/I vs. M/M for M883I). Login to comment 66 ABCA1 p.Arg219Lys After careful review, 47 articles involving 58 studies (42 studies for R219K polymorphism and 16 studies for M883I polymorphism) met the inclusion criteria and were selected in this meta-analysis [2-48]. Login to comment 67 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, 12551 AS cases and 19548 controls were included to assess the association between the variant and AS risk [2-41]. Login to comment 76 ABCA1 p.Arg219Lys Quantitative Synthesis For the ABCA1 R219K polymorphism, 42 studies were combined. Login to comment 77 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys The overall results showed evidence of significant association between the ABCA1 R219K polymorphism and the susceptibility to AS, suggesting that the ABCA1 R219K polymorphism was a protective role for AS (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). Login to comment 88 ABCA1 p.Arg219Lys Overall, the corresponding pooled ORs were not materially altered, either for the ABCA1 R219K polymorphism or for M883I polymorphism. Login to comment 91 ABCA1 p.Arg219Lys Heterogeneity Analysis For the ABCA1 R219K polymorphism, significant heterogeneity existed in the overall comparisons (for allelic model: PQ,0.01, I2 = 77.4%; for additive model: PQ,0.01, I2 = 67.9%; for recessive model: PQ,0.01, I2 = 64.2%; for dominant model: PQ,0.01, I2 = 69.7%). Login to comment 95 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, heterogeneity can be explained by the subtype of atherosclerotic diseases (allelic model: PT2 = 0.013, additive model: PT2 = 0.034, and recessive model: PT2 = 0.017) and study type (dominant model: PT4 = 0.037). Login to comment 101 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, visual inspection of the funnel plot (Fig. 4: K allele vs. R allele) displays asymmetrical distribution of OR estimations, suggesting significant publication bias. Login to comment 105 ABCA1 p.Arg219Lys In addition to the above analyses, we also calculated the Nfs (for the ABCA1 R219K polymorphism, Nfs = 133 for allelic model, Nfs = 146 for additive model, Nfs = 75 for recessive model, and Nfs = 49 for dominant model; for the ABCA1 M883I polymorphism, Nfs = 50 for allelic model), which reflected the minimum number of non-significant studies that would lead to the P-value to non-significant (P.0.05). Login to comment 106 ABCA1 p.Arg219Lys Discussion To the best of our knowledge, this is the first comprehensive meta-analysis to date investigating the associations between the ABCA1 R219K and M883I polymorphisms and AS risk. Login to comment 107 ABCA1 p.Arg219Lys Forty-two studies investigating the association between the ABCA1 R219K polymorphism and AS risk were combined [241], and 16 studies investigating the association between the ABCA1 M883I polymorphism and AS risk were combined Figure 1. Login to comment 111 ABCA1 p.Arg219Lys Study Source of Sample size HWE Position First author Year Country Ethnicity type Disease controls (case/ control) Genotypes distribution (case/control) Y/N(P) Score R219K R/R R/K K/K R K Clee 2001 Canada Caucasians CS CAD HB 432/358 248/176 170/160 14/22 666/512 198/204 Y(0.067) 6 Brousseau 2001 USA Caucasians CCS CAD PB 1014/1013 454/543 484/402 76/68 1392/1488 636/538 Y(0.580) 7 Cenarro 2003 Spain Caucasians CCS CAD HB 216/158 123/72 78/71 15/15 324/215 108/101 Y(0.676) 6 Evans 2003 Germany Caucasians CCS CAD HB 114/629 72/337 35/245 7/47 179/919 49/339 Y(0.789) 7 Harada 2003 Japan Asian CCS CAD HB 273/137 73/31 139/73 61/33 285/135 261/139 Y(0.440) 6 Wang 2004 China Asian CCS CAD PB 222/278 79/76 94/125 49/77 252/277 192/279 Y(0.093) 7 Zhao 2004 China Asian CCS CAD PB 236/251 96/80 111/123 29/48 303/283 169/219 Y(0.953) 8 Wang-a 2004 China Asian CCS IS PB 58/60 23/21 27/34 8/5 73/76 43/44 Y(0.088) 7 Wang-b 2004 China Asian CCS IS PB 58/60 19/14 35/36 4/10 73/64 43/56 Y(0.112) 7 Xiao 2004 China Asian CCS IS PB 379/351 149/112 172/172 58/67 470/396 288/306 Y(0.947) 8 Woll 2005 USA Caucasians CCS CAD PB 838/257 450/115 327/112 61/30 1227/342 449/172 Y(0.732) 6 Cui 2005 China Asian CCS IS PB 96/90 15/21 35/45 46/24 65/87 127/93 Y(0.992) 7 Whiting 2005 USA Mixed CS CAD HB 2468/834 1298/449 975/318 195/67 3571/1216 1365/452 Y(0.313) 6 Sun 2005 China Asian CCS CAD PB 224/248 105/62 85/129 34/57 295/253 153/243 Y(0.521) 8 Li 2005 China Asian CCS CAD PB 264/278 104/83 116/132 44/63 324/298 204/258 Y(0.449) 7 Chang 2005 China Asian CCS CAD PB 178/83 66/17 75/22 37/44 207/56 149/110 N(0.000) 7 Wang 2006 China Asian CCS CAD PB 396/417 158/124 174/198 64/95 490/446 302/388 Y(0.350) Wang 2006 China Asian CCS CAD HB 150/139 61/47 69/53 20/39 191/147 109/131 N(0.006) 6 Wang 2006 China Asian CCS CAD PB 234/198 108/67 105/101 21/30 321/235 147/161 Y(0.422) 8 Cha 2006 China Asian CCS CAD PB 112/108 47/34 53/52 12/22 147/120 77/96 Y(0.795) 7 Wu 2006 China Asian CCS CAD PB 67/20 26/2 30/7 11/11 82/11 52/29 Y(0.585) 6 Mart &#b4;n 2006 Spain Caucasians CS MI HB 100/100 48/49 42/40 10/11 138/138 62/62 Y(0.516) 6 Andrikovics -a 2006 Hungary Caucasians CCS IS PB 244/193 131/97 84/73 29/23 346/267 142/119 Y(0.116) 7 Andrikovics -b 2006 Hungary Caucasians CCS CAD PB 150/193 84/97 55/73 11/23 223/267 77/119 Y(0.116) 7 Yu 2008 China Asian CCS MI PB 49/72 29/24 18/35 2/13 76/83 22/61 Y(0.969) 7 Zhang 2008 China Asian CCS IS PB 177/234 43/40 87/129 47/65 173/209 181/259 Y(0.078) 7 Wang 2008 China Asian CCS CAD HB 111/75 30/17 54/41 27/17 114/75 108/75 Y(0.419) 6 Zhang 2008 China Asian CCS MI PB 162/186 71/49 65/93 26/44 207/191 117/181 Y(0.992) 8 Balcerzyk 2008 Poland Caucasians CCS CAD PB 178/180 90/91 68/78 20/11 248/260 108/100 Y(0.283) 6 Frikke-Schmidt 2008 Denmark Caucasians CS CAD PB 1107/7858 603/4260 429/3032 75/566 1635/ 11552 579/4164 Y(0.405) 7 Porchay-Balde &#b4;relli 2009 France Caucasians CS CAD HB 223/2906 106/1491 102/1183 15/232 314/4165 132/1647 Y(0.901) 6 Li 2009 China Asian CCS CAD PB 365/246 140/92 170/116 55/38 450/300 280/192 Y(0.886) 8 Shi 2009 China Asian CCS CAD HB 132/157 49/53 60/66 23/38 158/172 106/142 Y(0.058) 7 Doosti 2009 Iran Asian CCS CAD HB 207/94 71/17 77/38 59/39 219/72 195/116 Y(0.161) 6 Guo 2010 China Asian CCS CAD PB 71/83 30/29 37/38 4/16 97/96 45/70 Y(0.576) 7 Xu 2011 China Asian CCS CAD PB 246/109 95/31 128/53 23/25 318/115 174/103 Y(0.798) 8 Yuan 2011 China Asian CCS CAD PB 60/55 22/16 28/21 10/18 72/53 48/57 Y(0.081) 7 Yi 2011 China Asian CCS IS PB 240/240 36/45 97/109 107/86 169/199 311/281 Y(0.319) 7 Xue 2012 China Asian CCS CAA, IS PB 182/229 70/62 91/118 21/49 231/242 133/216 Y(0.608) 8 Wang 2012 China Asian CCS CAD PB 141/109 63/31 63/53 15/25 189/115 93/103 Y(0.798) 7 Li 2012 China Asian CCS MI PB 150/100 52/30 74/48 24/22 178/108 122/92 Y(0.735) 7 Xia 2012 China Asian CCS CAD HB 227/162 96/51 107/78 24/33 299/180 155/144 Y(0.750) 6 [14,15,22,23,29,30,42-48]. Login to comment 112 ABCA1 p.Arg219Lys According to the GRADE approach, the quality of the evidence was very low in the ABCA1 R219K polymorphism. Login to comment 114 ABCA1 p.Arg219Lys The overall findings showed that the ABCA1 R219K and M883I polymorphisms may exert an reduced risk effect on AS. Login to comment 115 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, the risk of developing AS in R allele carriers was 1.30-fold higher than those without R allele. Login to comment 118 ABCA1 p.Arg219Lys Therefore, it is reasonable to assume that the ABCA1 R219K K allele and M883I I allele are the protective factors for the development of AS. Login to comment 120 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, significant associations were found between this variant and the susceptibility to AS in the Asians group, CAD group, population-based group, hospital-based group and the subgroup of case-control study, respectively. Login to comment 121 ABCA1 p.Arg219Lys These results further strengthened the conclusion that the ABCA1 R219K K allele was a protective factor for AS. Login to comment 137 ABCA1 p.Arg219Lys For Caucasians, we did not find significant association between the ABCA1 R219K and M883I polymorphisms and AS risk. Login to comment 138 ABCA1 p.Arg219Lys In fact, the minor allele frequencies (MAF) of ABCA1 R219K and M883I are low among utah residents with Northern and Western European ancestry (CEU) (MAF = 0.210 and 0.133 in HapMap CEU) [64]. Login to comment 139 ABCA1 p.Arg219Lys However, the ABCA1 R219K and M883I polymorphisms are common among Han Chinese in Beijing, China (CHB) and Japanese in Tokyo, Japan (JPT) (MAF = 0.453/0.434 and 0.255/0.438, respectively) [64]. Login to comment 145 ABCA1 p.Arg219Lys As for the ABCA1 R219K polymorphism, the corresponding pooled ORs were not materially altered in all comparisons. Login to comment 147 ABCA1 p.Arg219Lys Meta-analyses of ABCA1 R219K and M883I polymorphisms and risk of AS in each subgroup. Login to comment 148 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Allelic model Additive model Recessive model Dominant model Position SS (case/control) OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value OR (95%CI) P value Overall analysis R219K 12551/19548 0.77[0.71,0.84] ,0.01 0.60[0.51,0.71] ,0.01 0.69[0.60,0.80] ,0.01 0.74[0.66,0.83] ,0.01 M883I 4224/13462 0.85[0.77,0.95] ,0.01 0.79 [0.61,1.01] 0.06 0.92[0.74,1.13] 0.42 0.86[0.72,1.02] 0.08 Subgroup analysis based on ethnicity R219K (C) 4616/13845 0.91[0.80,1.04] 0.16 0.83[0.65,1.06] 0.14 0.87[0.72,1.05] 0.14 0.90[0.76,1.07] 0.23 R219K (A) 7935/5703 0.71[0.64,0.79] ,0.01 0.52[0.42,0.63] ,0.01 0.62[0.52,0.75] ,0.01 0.66[0.59,0.74] ,0.01 M883I (C) 2067/11556 0.94[0.78,1.12] 0.48 1.24[0.67,2.29] 0.50 1.29[0.70,2.38] 0.41 1.05[0.86,1.28] 0.66 M883I (A) 2157/1906 0.82[0.72,0.93] ,0.01 0.72[0.54,0.95] 0.02 0.88[0.70,1.09] 0.25 0.75[0.61,0.91] ,0.01 Subgroup analysis based on type of diseases R219K (CAD) 11117/18091 0.74[0.67,0.82] ,0.01 0.56[0.47,0.67] ,0.01 0.64[0.55,0.74] ,0.01 0.72[0.64,0.82] ,0.01 R219K (IS) 1434/1457 0.94[0.75,1.17] 0.58 0.86[0.55,1.35] 0.51 1.00[0.69,1.45] 1.00 0.82[0.65,1.02] 0.08 M883I (CAD) 3890/13257 0.82[0.74,0.90] ,0.01 0.73[0.57,0.94] 0.01 0.88[0.71,1.09] 0.24 0.81[0.68,0.97] 0.02 M883I (IS) 334/205 1.43[1.02,2.02] 0.04 2.79[0.95,8.21] 0.06 2.51[0.86,7.29] 0.09 1.40[0.94,2.07] 0.10 Subgroup analysis based on source of controls R219K (PB) 7898/13799 0.76[0.67,0.85] ,0.01 0.58[0.47,0.72] ,0.01 0.68[0.56,0.82] ,0.01 0.72[0.62,0.83] ,0.01 R219K (HB) 4653/5749 0.81[0.71,0.92] ,0.01 0.65[0.51,0.82] ,0.01 0.72[0.59,0.87] ,0.01 0.80[0.68,0.94] ,0.01 M883I (PB) 3612/10285 0.87[0.78,0.97] 0.01 0.77[0.58,1.04] 0.09 0.91[0.73,1.13] 0.39 0.86[0.72,1.04] 0.11 M883I (HB) 612/3177 0.75[0.52,1.08]a 0.13 0.93[0.45,1.90] 0.84 1.02[0.50,2.09] 0.95 0.88[0.51,1.55] 0.67 Subgroup analysis based on study type R219K (CS) 4330/12056 0.97[0.88,1.07] 0.55 0.91[0.75,1.10] 0.32 0.91[0.76,1.07] 0.25 0.99[0.87,1.12] 0.84 R219K (CCS) 8221/7492 0.74[0.67,0.82] ,0.01 0.57[0.47,0.68] ,0.01 0.67[0.57,0.78] ,0.01 0.70[0.62,0.79] ,0.01 M883I (CS) 1673/11346 0.87[0.71,1.08] 0.21 1.05[0.54,2.04] 0.89 1.10[0.56,2.14] 0.78 1.04[0.80,1.36] 0.77 M883I (CCS) 2551/2116 0.85[0.75,0.97] 0.01 0.75[0.56,1.02] 0.06 0.90[0.72,1.12] 0.34 0.79[0.65,0.95] 0.01 Sensitivity analysis R219K (BS) 7061/14128 0.76[0.68,0.85] ,0.01 0.60[0.49,0.73] ,0.01 0.69[0.58,0.82] ,0.01 0.72[0.62,0.83] ,0.01 R219K (BH) 12223/19326 0.79[0.72,0.86] ,0.01 0.62[0.53,0.74] ,0.01 0.73[0.64,0.83] ,0.01 0.75[0.67,0.84] ,0.01 R219K (BT) 11647/18669 0.78[0.71,0.85] ,0.01 0.60[0.51,0.71] ,0.01 0.70[0.61,0.80] ,0.01 0.74[0.66,0.83] ,0.01 M883I (BS) 3255/10125 0.87[0.77,0.99] 0.03 0.77[0.54,1.10] 0.16 0.90[0.71,1.16] 0.42 0.87[0.71,1.05] 0.15 M883I (BH) 3571/13041 0.88[0.79,0.98] 0.02 0.80[0.58,1.10] 0.17 0.92[0.73,1.15] 0.44 0.84[0.71,0.98] 0.03 M883I (BT) 3870/13084 0.84[0.76,0.92] ,0.01 0.75[0.58,0.95] 0.02 0.89[0.72,1.10] 0.29 0.85[0.71,1.01] 0.07 A: Asians, C: Caucasians, PB: population-based, HB: hospital-based. Login to comment 156 ABCA1 p.Arg219Lys Significant heterogeneity existed in the present meta-analysis, either for the ABCA1 R219K polymorphism or for the ABCA1 M883I polymorphism. Login to comment 158 ABCA1 p.Arg219Lys For the ABCA1 R219K polymorphism, the heterogeneity can be explained by the subtype of atherosclerotic diseases (CAD and IS) and study type (case-control and cohort study). Login to comment 168 ABCA1 p.Arg219Lys Forest plot for ABCA1 R219K polymorphism and AS risk in the allelic model (K allele vs. R allele). Login to comment 172 ABCA1 p.Arg219Lys Funnel plots for ABCA1 R219K and M883I polymorphisms and AS risk. Login to comment 173 ABCA1 p.Arg219Lys K allele vs. R allele for ABCA1 R219K polymorphism. Login to comment 179 ABCA1 p.Arg219Lys In conclusion, the present meta-analysis suggested that the ABCA1 R219K and M883I polymorphisms were associated with the susceptibility to AS, especially in Asians. Login to comment 182 ABCA1 p.Arg219Lys Supporting Information Figure S1 Forest plot for ABCA1 R219K polymorphism and AS risk in the additive model (K/K vs. R/R). Login to comment 183 ABCA1 p.Arg219Lys (TIF) Figure S2 Forest plot for ABCA1 R219K polymorphism and AS risk in the rssive model (K/K vs. R/K+R/R). Login to comment 184 ABCA1 p.Arg219Lys (TIF) Figure S3 Forest plot for ABCA1 R219K polymorphism and AS risk in the dominant model (K/K+R/K vs. R/R). Login to comment 190 ABCA1 p.Arg219Lys (DOC) Table S3 The meta-regression results for the association of the ABCA1 R219K polymorphism and AS. Login to comment