ABCMdb

PMID: 25104170

Liu N, Hou M, Ren W, Cao J, Wu H, Zhou W
The R219K polymorphism on ATP-binding cassette transporter A1 gene is associated with coronary heart disease risk in Asia population: evidence from a meta-analysis.
Cell Biochem Biophys. 2015 Jan;71(1):49-55. doi: 10.1007/s12013-014-0161-8., [PubMed]

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0 ABCA1 p.Arg219Lys ORIGINAL PAPER The R219K Polymorphism on ATP-Binding Cassette Transporter A1 Gene is Associated with Coronary Heart Disease Risk in Asia Population: Evidence from a Meta-Analysis Nannan Liu ߦ Mingxiao Hou ߦ Weidong Ren ߦ Junying Cao ߦ Hongli Wu ߦ Weiwei Zhou Published online: 8 August 2014 &#d3; Springer Science+Business Media New York 2014 Abstract A number of case-control studies have been conducted to investigate the relationship between the ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms and risk of coronary heart disease (CHD). Login to comment 6 ABCA1 p.Arg219Lys Statistically significant association between ABCA1 gene R219K polymorphism and increased CHD risk was found in total population analyses in all four genetic comparison models (ORC vs. T 1.19, 95 % CI 1.07-1.31; P = 0.001; ORHomozygote model 1.28, 95 % CI 1.07-1.52; P = 0.007; ORRecessive genetic model 1.22, 95 % CI 1.04-1.44, P = 0.015; ORDominant model 1.21, 95 % CI 1.07-1.35; P = 0.001). Login to comment 8 ABCA1 p.Arg219Lys ABCA1 R219K polymorphism is associated with CHD susceptibility, and individuals with ABCA1 have a significantly higher risk of cancer particularly in Asians. Login to comment 9 ABCA1 p.Arg219Lys Keywords ABCA1 R219K CHD Asians Introduction Coronary heart disease (CHD) is one of the major causes of mortality, being responsible for approximately 30 % of deaths worldwide [34]. Login to comment 23 ABCA1 p.Arg219Lys lysine substitution at exon 7 (R219K, rs2230806) and isoleucine ? Login to comment 24 ABCA1 p.Ile883Met methionine substitution in exon 18 (I883M, rs4149313) were studied widely for their association with CHD susceptibility [12, 23]. Login to comment 25 ABCA1 p.Arg219Lys To date, many case-control studies have been carried out to investigate the relationship between ABCA1 R219K polymorphism and the risk of developing CHD, but the results were conflicting or inconclusive. Login to comment 27 ABCA1 p.Arg219Lys Therefore, there is a role for meta-analysis in pooling these studies, particularly to clarify the effect of R219K polymorphism on ABCA1 gene with the risk of CHD. Login to comment 32 ABCA1 p.Arg219Lys The inclusion criteria were (1) case-control studies which evaluated the association of R219K polymorphism on ABCA1 with CHD risk; (2) based on unrelated cancer individuals; (3) sufficient published genotype data for estimating an odds ratio (OR) with 95 % confidence interval (CI); and (4) genotype distribution of the control population reported was in Hardy-Weinberg equilibrium (HWE). Login to comment 53 ABCA1 p.Arg219Lys Subgroup analyses based on cancer type showed ABCA1-R219K variant was significantly associated with increased risk of CHD and cardiovascular disease (Table 3). Login to comment 55 ABCA1 p.Arg219Lys Table 1 Characteristics of studies included in this meta-analysis References Ethnicity (country) Characteristics of cases Characteristics of controls HWE&#e0; Qi et al. [24] Asians 109 histologically confirmed malignant mesothelioma cases 252 population controls Yes Shi et al. [25] Asians 995 histologically confirmed breast cancer cases 1,004 cancer-free controls Yes Sun et al. [27] Asians 234 bladder cancer patients 253 cancer-free controls Yes Tsai et al. [30] Asians 43 histologically confirmed breast cancer cases 31 healthy volunteers Yes Harada et al. [14] Asians 456 histologically confirmed gastric cancer patients 507 healthy controls Yes Tan et al. [28] Asians 294 histologically confirmed lung cancer cases 288 cancer-free controls Yes Zhang et al. [35] Asians 350 histologically confirmed lung cancer cases 350 cancer-free controls Yes Mart &#b4;n et al. [19] Caucasians 109 histologically confirmed lung cancer cases 110 cancer-free controls Yes Andrikovics et al. [1] Caucasians 530 bladder cancer patients 556 healthy controls Yes Jensen et al. [15] Caucasians 247 breast cancer cases 380 healthy controls Yes Nebel et al. [20] Caucasians 1,024 histologically confirmed lung cancer cases 1,118 cancer-free controls Yes Evans and Beil [11] Caucasians 710 lung cancer patients 710 cancer-free controls Yes Frikke-Schmidt et al. [12] Caucasians 405 histologically confirmed ESCC cases 478 cancer-free controls Yes ESCC esophageal squamous cell carcinoma; &#e0; HWE Hardy-Weinberg equilibrium Table 2 Distribution of ABCA1 and R219K genotypes and alleles among cancer cases and controls in the meta-analysis References Genotype Allele PHWE T/T (n) T/C (n) C/C (n) T (n) C (n) Case Control Case Control Case Control Case Control Case Control Mart &#b4;n et al. [19] 75 104 99 144 27 47 249 352 153 238 0.81 Qi et al. [24] 766 817 210 179 19 8 1,742 1,813 248 195 0.60 Frikke-Schmidt et al. [12] 174 178 56 73 4 2 404 429 64 77 0.06 Andrikovics et al. [1] 20 15 19 13 4 3 59 43 27 19 0.94 Shi et al. [25] 155 188 219 238 82 81 529 614 383 400 0.70 Tsai et al. [30] 251 250 40 37 3 1 542 537 46 39 0.76 Sun et al. [27] 264 291 75 55 11 4 603 637 97 63 0.45 Jensen et al. [15] 37 40 53 52 19 18 127 132 91 88 0.87 Zak and co-authors [2] 174 187 266 275 90 94 614 649 446 463 0.68 Nebel et al. [20] 90 134 107 187 50 59 287 455 207 305 0.64 Harada et al. [14] 783 924 223 182 18 12 1,789 2,030 259 206 0.37 Tan et al. [28] 500 558 198 148 12 4 1,198 1,264 222 156 0.08 Zhang et al. [35] 305 384 94 89 6 5 704 857 106 99 0.95 Caucasians 551 668 763 909 272 302 1,865 2,245 1,307 1,513 0.81 Asians 3,043 3,402 896 763 73 36 6,982 7,567 1,042 835 0.34 Total 3,594 4,070 1,659 1,672 345 338 8,847 9,812 2,349 2,348 \0.01 PHWE P values for Hardy-Weinberg equilibrium The between-study heterogeneity was not obvious in most comparisons except the Allele gene model (R vs. K) comparison analysis based on total studies (I2 = 50.4 %). Login to comment 63 ABCA1 p.Arg219Lys The present meta-analysis of 13 case-control studies, involving a total of 5,898 cancer cases and 6,080 controls, provides the most comprehensive assessment so far of the association between ABCA1-R219K polymorphism and cancer risk. Login to comment 64 ABCA1 p.Arg219Lys The findings of this meta-analysis indicate that variant homozygote CC of ABCA1-R219K is significantly associated with increased cancer risk (OR = 1.28, 95 % CI 1.07-1.52; P = 0.007). Login to comment 71 ABCA1 p.Arg219Lys Therefore, we first stratified studies Fig. 1 Flow chart of selection of studies for inclusion in the meta-analysis Fig. 2 Forest plots of pooled OR with 95 % CI for associations between ABCA1 and R219K polymorphism and CHD risk (The size of the data markers is inversely proportional to the variance of the log ORs; horizontal lines represent the 95 % CIs. Login to comment 74 ABCA1 p.Arg219Lys One explanation about how ABCA1 R219K polymorphism modifies the risk of CHD is that ABCA1 may influence the plasma lipid levels. Login to comment 76 ABCA1 p.Arg219Lys Only the R219K was significantly associated with HDL-C concentration and CAD risk. Login to comment 79 ABCA1 p.Arg219Lys It is probable that the protective function of R219K polymorphism is not only explained by increased plasma HDL-C level, but also by ABCA1 polymorphism. Login to comment 82 ABCA1 p.Arg219Lys Another probable mechanism is that R219K polymorphism induces the activity of ABCA1 protein, which mediates cholesterol efflux from peripheral cells back to liver independent of plasma HDL-C levels. Login to comment 91 ABCA1 p.Arg219Lys In additional, Cenaro et al. reported that R219K variant appeared to be more protective for smokers and exsmokers than non-smokers in the premature CHD group. Login to comment 96 ABCA1 p.Arg219Lys Our meta-analysis supports an association of ABCA1 R219K polymorphism with CHD in Asians. Login to comment 99 ABCA1 p.Arg219Lys In subgroup analyses, evidence was obtained to suggest different risk effects of R219K between populations of Caucasians and Asians. Login to comment