ABCMdb

PMID: 23053993

Li YY, Zhang H, Qin XY, Lu XZ, Yang B, Chen ML
ATP-binding cassette transporter A1 R219K polymorphism and coronary artery disease in Chinese population: a meta-analysis of 5,388 participants.
Mol Biol Rep. 2012 Dec;39(12):11031-9. doi: 10.1007/s11033-012-2006-0. Epub 2012 Oct 9., [PubMed]

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0 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ATP-binding cassette transporter A1 R219K polymorphism and coronary artery disease in Chinese population: a meta-analysis of 5,388 participants Yan-yan Li ߦ Hui Zhang ߦ Xiao-yi Qin ߦ Xin-zheng Lu ߦ Bing Yang ߦ Ming-long Chen Received: 16 January 2012 / Accepted: 1 October 2012 / Published online: 9 October 2012 &#d3; Springer Science+Business Media Dordrecht 2012 Abstract The ATP-binding cassette transporter A1 (ABCA1) R219K gene polymorphism has been suggested to lower the risk of coronary artery disease (CAD). Login to comment 2 ABCA1 p.Arg219Lys Meta-analysis involving 2,730 CAD patients and 2,658 controls was performed to investigate the relationship between ABCA1 R219K gene polymorphism and CAD in Chinese population. Login to comment 5 ABCA1 p.Arg219Lys A significant association between ABCA1 R219K gene polymorphism and CAD was found in the Chinese population under the following genetic models: an allelic genetic model (OR 0.70, 95 % CI 0.62-0.78, P \ 0.00001), a recessive genetic model (OR 0.51, 95 % CI 0.41-0.64, P \ 0.00001), an additive genetic model (OR 0.816, 95 % CI 0780-0.855, P = 0), a dominant genetic model (OR 1.326, 95 % CI 1.232-1.427, P = 0), a homozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0), and a heterozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0). Login to comment 6 ABCA1 p.Arg219Lys The K allele of the ABCA1 R219K gene has a protective role for CAD risk in Chinese population and is possibly associated with decreased CAD susceptibility. Login to comment 7 ABCA1 p.Arg219Lys Keywords ATP-binding cassette transporter A1 R219K Gene polymorphism Coronary artery disease Chinese Introduction Coronary artery disease (CAD) is one of the leading causes of death. Login to comment 20 ABCA1 p.Arg219Lys R219K is a common variation in the ABCA1 gene-coding region. Login to comment 24 ABCA1 p.Arg219Lys [7] found that ABCA1 R219K polymorphism was associated with a higher HDL-C level in Asians and performed a protective role for CAD in both Asians and Caucasians. Login to comment 26 ABCA1 p.Arg219Lys They reported that the K allele of ABCA1 R219K polymorphism was a protective factor associated with decreased CAD susceptibility worldwide [8]. Login to comment 29 ABCA1 p.Arg219Lys Domestically, results of the widely researched topics of ABCA1 R219K gene polymorphism and CAD are still debatable [10, 11]. Login to comment 30 ABCA1 p.Arg219Lys Hence, the current meta-analysis on 2,730 CAD patients and 2,658 subjects was conducted to arrive at a decisive conclusion on the associations between ABCA1 R219K gene polymorphism and CAD in the Chinese population. Login to comment 33 ABCA1 p.Arg219Lys The studies had to comply with the following major criteria: (a) Evaluation of the ABCA1 R219K gene polymorphism and CAD in Chinese population; (b) CAD was diagnosed by coronary arteriography and clinical symptoms combined with electrocardiogram, echocardiography, treadmill exercise test, and myocardial perfusion imaging in emission computed tomography (ECT); (c) The individual study should be a case-control or cohort study published in an official journal; and (d) The individual study should agree with the Hardy-Weinberg equilibrium (HWE). Login to comment 45 ABCA1 p.Arg219Lys The odds ratios (ORs) corresponding to 95 % confidence intervals (CIs) were used to examine the association between ABCA1 R219K gene polymorphism and CAD. Login to comment 59 ABCA1 p.Arg219Lys Out of the 17 excluded studies, two were repeated publications, seven were of review character, and six were not associated with ABCA1 R219K gene polymorphism. Login to comment 63 ABCA1 p.Arg219Lys Pooled analyses A significant association between ABCA1 R219K gene polymorphism and CAD was found in the Chinese population under the following genetic models: an allelic genetic model (OR 0.70, 95 % CI 0.62-0.78, P \ 0.00001), a recessive genetic model (OR 0.51, 95 % CI 0.41-0.64, P \ 0.00001), an additive genetic model (OR 0.816, 95 % CI 0780-0.855, P = 0), a dominant genetic model (OR 1.326, 95 % CI 1.232-1.427, P = 0), a homozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0) and a heterozygote genetic model (OR 0.640, 95 % CI 0.575-0.712, P = 0). Login to comment 66 ABCA1 p.Arg219Lys The CAD group sample size (allelic genetic model, P = 0.015), KK genotype sample size of CAD group (KK1) (recessive genetic Fig. 1 Flow diagram of articles selection process for ABCA1 R219K gene polymorphism and CAD risk meta-analysis model, P = 0.014; homozygote genetic model, P = 0.014), RR genotype sample size of CAD group (RR1) (dominant genetic model, P = 0.004), and RK genotype sample size of CAD group (RK1) (heterozygote genetic model, P = 0.004) (additive genetic model, P = 0.013) possibly explained the heterogeneity. Login to comment 70 ABCA1 p.Arg219Lys No significant association was detected between ABCA1 R219K gene polymorphism and CAD in subgroup 1 (OR 0.85, 95 % CI 0.70-1.03, Pheterogeneity = 0.09, I2 = 58.4 %, P = 0.10. Login to comment 76 ABCA1 p.Arg219Lys No positive association was detected between ABCA1 R219K gene polymorphism and CAD in subgroup 1 (recessive genetic model, OR 0.78, 95 % CI 0.56-1.10, Pheterogeneity = 0.12, I2 = 53.4 %, P = 0.16) (homozygote genetic model, OR 0.812, 95 % CI 0.696-0.948, Pheterogeneity = 0.126, I2 = 51.7 %, P = 0.008). Login to comment 81 ABCA1 p.Arg219Lys A significant association was found between ABCA1 R219K gene polymorphism and CAD in the three subgroups (subgroup 1, OR 1.337, 95 % CI 1.199-1.491, Pheterogeneity = 0.005, I2 = 76.9 %, P = 0) (subgroup 2, OR 1.257, 95 % CI 1.081-1.462, Pheterogeneity = 0.760, I2 = 0 %, P = 0.003) (subgroup 3, OR 1.369, 95 % CI 1.198-1.564, Pheterogeneity = 0.215, I2 = 27.9 %, P = 0). Login to comment 86 ABCA1 p.Arg219Lys A significant association was found between ABCA1 R219K gene polymorphism Table 1 Characteristics of the investigated studies of the association between ABCA1 R291K gene polymorphism and coronary artery disease Author Year Region Ethnicity CAD Control Matching criteria Sample size (CAD/ control) P value of HWE RR RK KK RR RK KK Zhaoa 2004 Hunan Han 96 111 29 80 123 48 Age, sex, ethnicity, BMI 236/251 0.95 Lib 2005 Sichuan Han 158 174 64 124 198 95 Age, sex, ethnicity 396/417 0.35 Sunc 2005 Jiangsu Han 105 85 34 62 129 57 Ethnicity, BMI 224/248 0.52 Wangd 2006 Hebei Han 108 105 21 67 101 30 Age, sex, ethnicity, BMI 234/198 0.42 Zhae 2006 Guangdong Han 47 53 12 34 52 22 Age, sex, ethnicity 112/108 0.80 Lif 2008 Heilongjiang Han 140 170 55 92 116 38 Age, sex, ethnicity 365/246 0.89 Liug 2008 Gansu Han 29 39 3 57 60 28 Ethnicity 71/145 0.10 Wangh 2008 Zhejiang Han 85 161 75 67 155 72 Ethnicity 321/294 0.35 Yui 2008 Shanghai Han 29 18 2 24 35 13 Sex, ethnicity 49/72 0.97 Zhangj 2008 Zhejiang Han 71 65 26 49 93 44 Sex, ethnicity 162/186 0.99 Shik 2009 Hunan Han 49 60 23 53 66 38 Age, sex, ethnicity, BMI 132/157 0.54 Xial 2011 Guangxi Han 96 107 24 51 78 33 Age, sex, ethnicity, BMI 227/162 0.75 Xum 2011 Beijing Han 63 63 15 31 53 25 Ethnicity 141/109 0.80 Yuann 2011 Neimenggu Mongolian 22 28 10 16 21 18 Age, ethnicity 60/55 0.08 The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) geno-typing method and case-control study design were adopted in all of the above studies BMI body mass index a Ref. [10], b Ref. [16], c Ref. [17], d Ref. [18], e Ref. [19], f Ref. [20], g Ref. [21], h Ref. [11], i Ref. [22], j Ref. [23], k Ref. [24], l Ref. [25], m Ref. [26], n Ref. [27] and CAD in the three subgroups (heterozygote genetic model, subgroup 1, OR 0.916, 95 % CI 0.846-0.992, Pheterogeneity = 0.365, I2 = 0.8 %, P = 0.032; subgroup 2, OR 0.804, 95 % CI 0.734-0.881, Pheterogeneity = 0.105, I2 = 51.2 %, P = 0; subgroup 3, OR 0.863, 95 % CI 0.781-0.953, Pheterogeneity = 0.119, I2 = 40.8 %, P = 0.004) (additive genetic model, subgroup 1, OR 0.906, 95 % CI 0.844-0.971, Pheterogeneity = 0.085, I2 = 59.4 %, P = 0.006; subgroup 2, OR 0.762, 95 % CI 0.702-0.829, Pheterogeneity = 0.545, I2 = 0 %, P = 0; subgroup 3, OR 0.759, 95 % CI 0.695-0.829, Pheterogeneity = 0.398, I2 = 3.7 %, P = 0) (Table 2; Figs. Login to comment 91 ABCA1 p.Arg219Lys Discussion In the current meta-analysis of 2,730 CAD patients and 2,658 control subjects in Chinese population, the K allele of ABCA1 R219K was significantly associated with decreased CAD risk under allelic (OR 0.70), recessive (OR 0.51), additive (OR 0.816), dominant (OR 1.326), homozygote (OR 0.640), and heterozygote genetic model (OR 0.863). Login to comment 94 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys The association of ABCA1 R219K gene polymorphism and Table 2 Summary of meta-analysis of association of ABCA1 R219K polymorphism and CAD risk Genetic model Group analysis Pooled OR (95 % CI) P value Literature number CAD size Control size Pheterogeneity Allelic genetic model Whole population 0.70 (0.62-0.78) \0.00001* 14 2,730 2,658 0.030* Subgroup1: T1 [ 300 0.85 (0.70-1.03) 0.100 3 1,082 957 0.090 Subgroup2: 300 [ T1 [ 200 0.65 (0.57-0.75) \0.00001* 4 921 859 0.400 Subgroup3: T1 \ 200 0.63 (0.54-0.73) \0.00001* 7 727 842 0.470 Recessive genetic model Whole population 0.51 (0.41-0.64) \0.00001* 14 2,730 2,658 0.020* Subgroup1: KK1 [ 40 0.78 (0.56-1.10) 0.160 3 1,082 957 0.120 Subgroup2: 20 \ KK1 \ 40 0.50 (0.40-0.63) \0.00001* 6 1,215 1,202 0.970 Subgroup3: KK1 \ 20 0.29 (0.19-0.43) \0.00001* 5 433 489 0.630 Dominant genetic model Whole population 1.326 (1.232-1.427) 0.000* 14 2,730 2,658 0.049* Subgroup1: RR1 [ 100 1.337 (1.199-1.491) 0.000* 4 784 707 0.005* Subgroup2: 80 \ RR1 \ 100 1.257 (1.081-1.462) 0.003* 3 1,219 1,109 0.760 Subgroup3: RR1 \ 80 1.369 (1.198-1.564) 0.000* 7 727 842 0.215 Homo genetic model Whole population 0.640 (0.575-0.712) 0.000* 14 2,730 2,658 0.016* Subgroup1: KK1 [ 40 0.812 (0.696-0.948) 0.008* 3 1,082 957 0.126 Subgroup2: 20 \ KK1 \ 40 0.575 (0.487-0.678) 0.000* 6 1,215 1,202 0.728 Subgroup3: KK1 \ 20 0.426 (0.310-0.587) 0.000* 5 433 489 0.495 Hetero genetic model Whole population 0.863 (0.819-0.908) 0.000* 14 2,730 2,658 0.046* Subgroup1: RK1 [ 150 0.916 (0.846-0.992) 0.032* 3 1,082 957 0.365 Subgroup2: 150 [ RK1 [ 70 0.804 (0.734-0.881) 0.000* 4 921 859 0.105 Subgroup3: RK1 \ 70 0.863 (0.781-0.953) 0.004* 7 727 842 0.119* Additive genetic model Whole population 0.816 (0.780-0.855) 0.000* 14 2,730 2,658 0.013* Subgroup1: RK1 [ 150 0.906 (0.844-0.971) 0.006* 3 1,082 957 0.085 Subgroup2: 150 [ RK1 [ 70 0.762 (0.702-0.829) 0.000* 4 921 859 0.545 Subgroup3: RK1 \ 70 0.759 (0.695-0.829) 0.000* 7 727 842 0.398 CI confidence interval; OR odds ratio; MI size the total number of MI cases; control size the total number of control group; homo genetic model homozygote genetic model; hetero genetic model heterozygote genetic model; T1 total CAD group sample size; KK1 KK1 genotype sample size of CAD group; RR1 RR1 genotype sample size of CAD group; RK1 RK1genotype sample size of CAD group *P \ 0.05 CAD distinctly weakened in the three studies with T1 [ 300. Login to comment 97 ABCA1 p.Arg219Lys The association of ABCA1 R219K gene polymorphism with CAD was also distinctly impaired in the three studies with KK1 [ 40. Login to comment 100 ABCA1 p.Arg219Lys Results of the current meta-analysis indicated that the K allele of ABCA1 R219K gene has a protective effect on CAD risk in the Chinese population. Login to comment 112 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Recent studies have Fig. 2 Forest plot of coronary artery disease associated with ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism under an allelic genetic model (distribution of K allelic frequency of ABCA1 R219K gene) stratified by CAD sample size (T1) Fig. 3 Forest plot of coronary artery disease associated with ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism under a recessive genetic model (KK vs. RK ? Login to comment 113 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys RR) stratified by KK1 genotype sample size Fig. 4 Funnel plot for studies of the association of coronary artery disease and ATP-binding cassette transporter A1 (ABCA1) R219K polymorphism under the allelic genetic model (distribution of K allelic frequency of ABCA1 R219K gene). Login to comment 118 ABCA1 p.Arg219Lys R219K is the familiar variation of ABCA1 gene. Login to comment 119 ABCA1 p.Arg219Lys Studies on the gene polymorphism of R219K focused on the association between atherosclerosis and lipid metabolism. Login to comment 120 ABCA1 p.Arg219Lys The R219K mutation correlated with increased HDL-C, alleviated atherosclerosis, and decreased CAD risk [30, 31]. Login to comment 122 ABCA1 p.Arg219Lys The association of the K allele of the ABCA1 R219K gene with decreased CAD susceptibility was further verified in the current meta-analysis. Login to comment 123 ABCA1 p.Arg219Lys In addition, the study suggests that the distribution of K allele of the ABCA1 R219K gene indicated a protective factor for CAD risk. Login to comment 127 ABCA1 p.Arg219Lys The R219K genotype distribution, K allele frequency, and carriers were confirmed to be different among different ethnicities [32]. Login to comment 133 ABCA1 p.Arg219Lys Thus, the relationship between ABCA1 R219K gene polymorphism and CAD in the Chinese population cannot be elucidated clearly as that in the current meta-analysis even if they obtained a positive conclusion. Login to comment 135 ABCA1 p.Arg219Lys Large-scale research on arteriosclerosis protection of R219K remains inadequate. Login to comment 137 ABCA1 p.Arg219Lys Finally, the current meta-analysis suggested that the distribution of the K allele frequency of the ABCA1 R219K gene may protect the Chinese population from CAD risks. Login to comment