ABCMdb

PMID: 21300560

Jiang Z, Zhou R, Xu C, Feng G, Zhou Y
Genetic variation of the ATP-binding cassette transporter A1 and susceptibility to coronary heart disease.
Mol Genet Metab. 2011 May;103(1):81-8. Epub 2011 Jan 22., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCA1 p.Arg219Lys Overall, significantly decreased CHD risk was associated with 219 K allele of R219K polymorphism when all studies were pooled into the meta-analysis. Login to comment 7 ABCA1 p.Ile883Met However, no significant results were observed for I883M polymorphism of ABCA1 in all genetic models. Login to comment 8 ABCA1 p.Arg219Lys In conclusion, this meta-analysis suggests that K allele of ABCA1 R219K polymorphism is a protective factor associated with decreased CHD susceptibility, but these associations vary in different ethnic populations. Login to comment 33 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Among them, two common polymorphisms in the coding region, which lead to a arginine→lysine substitution at exon 7 (R219K, rs2230806) and isoleucine→methionine substitution in exon 18 (I883M, rs4149313) were studied widely for their association with CHD susceptibility [8,9]. Login to comment 35 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys In consideration of the extensive role of ABCA1 in the development of CHD, we carried out a comprehensive meta-analysis on all eligible case-control studies to estimate the overall CHD risk of ABCA1 R219K and I883M polymorphisms as well as to quantify the between-study heterogeneity and potential bias. Login to comment 38 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Literature search and data extraction Genetic association studies published before the end of November 2010 on CHD and the R219K and I883M polymorphisms in the ABCA1 were sought through a search of PubMed, Web of Science, EMBASE, and CNKI (Chinese National Knowledge Infrastructure) database without language restrictions. Login to comment 49 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys The strength of association between R219K and I883M polymorphisms of ABCA1 and CHD risk was assessed by OR with the corresponding 95% confidence interval (CI). Login to comment 69 ABCA1 p.Arg219Lys For the R219K polymorphism, 27 studies involved a total of 12,960 cases and 26,834 controls. Login to comment 70 ABCA1 p.Ile883Met For the I883M polymorphism, 12 studies involved a total of 7189 cases and 23,350 controls. Login to comment 75 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met 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 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 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 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 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys of cases/ controls Mean age of cases/ controls Gender component in cases/controls (% male) Diagnostic criterion Outcome Definition of control Control source Genotyping method HWE for control Qi [15] 2010 R219K Chinese 173/389 60.0/61.0 70.3/57.9 ≥50% stenosis CAD CAD- HB RFLP Y Doosti [16] 2010 R219K Iranian 207/84 49.1/55.1 83.1/59.6 NA CAD CAD- HB RFLP N Shi [17] 2009 R219K Chinese 132/157 61.7/61.1 NA/NA NA CHD CAD- HB RFLP Y Wang [18] 2009 R219K Chinese 150/139 53.5/51.1 80.0/64.7 ≥50% stenosis CHD CHD- HB RFLP N Porchay-Baldérelli [8] 2009 R219K, I883M French 482/2647 68.0/65.2 79.7/71.8 NA CHD CHD- PB allele-specific PCR Y Li [19] 2009 R219K Chinese 365/246 63.0/61.0 66.4/45.9 ≥50% stenosis CHD Healthy PB RFLP Y Zhang [20] 2008 R219K Chinese 162/186 68.3/63.5 74.7/66.1 ≥50% stenosis CHD CHD- HB RFLP Y Ni [21] 2008 R219K Chinese 260/248 63.5/62.1 64.6/66.1 ≥50% stenosis CHD CHD- HB RFLP N Liu [22] 2008 R219K Chinese 71/155 58.0/57.0 52.1/55.5 NA CHD Healthy, CHD- HB, PB RFLP Y Frikke-Schmidt [9] 2008 R219K, I883M Danish 2039/15,851 NA/NA NA IHD IHD- PB TaqMan Y Wang [23] 2008 R219K Chinese 321/294 NA/NA NA/NA ≥50% stenosis CHD CHD- HB RFLP Y Balcerzyk [24] 2007 R219K Pole 178/180 43.8/35.0 65.7/71.1 ≥50% stenosis CAD CAD- PB RFLP Y Jensen [25] 2007 I883M American 259/930 62.0/54.3 0/0 WHO CHD CHD- PB Probe Y Tsai [26] 2007 I883M Chinese 205/201 62.9/51.9 78.0/51.0 ≥50% stenosis CAD CAD- PB RFLP Y Nebel [27] 2007 I883M German 1090/728 NA/NA NA/NA ≥70% stenosis CHD Healthy PB TaqMan Y Andrikovics [28] 2006 R219K, I883M German 150/193 53.4/35.3 68.4/48.2 ≥50% stenosis CHD CHD- PB Probe Y Wang [29] 2006 R219K Chinese 234/198 64.9/62.5 61.1/59.1 ≥50% stenosis CHD CHD- HB RFLP Y Martin [30] 2006 R219K, I883M Spanish 100/100 NA/NA 100/100 NA MI CHD- HB NA Y Li [31] 2005 R219K Chinese 394/417 60.1/59.4 59.8/59.5 ≥50% stenosis CHD Healthy PB RFLP Y Woll [32] 2005 R219K American 838/257 49.5/48.3 NA/NA NA CAD Healthy PB RFLP Y Sun [33] 2005 R219K, I883M Chinese 224/248 63.7/59.6 66.9/55.2 ≥50% stenosis CHD CHD- PB RFLP Y Whiting [34] 2004 R219K American 2468/834 65.0/59.0 60.0/46.0 ≥70% stenosis CAD CAD- HB RFLP Y Wang [35] 2004 R219K Chinese 222/278 62.4/62.2 54.9/50.7 NA CHD Healthy PB RFLP Y Tregouet [36] 2004 R219K, I883M British 750/722 56.3/57.3 67.0/NA NA MI CHD- PB BigDye Y Zhao [37] 2004 R219K Chinese 236/251 NA/NA NA/NA NA CHD Healthy PB RFLP Y Bertolini [38] 2004 R219K Italian 97/97 53.9/53.8 58.8/58.8 ≥50% stenosis CAD CAD- PB RFLP Y Harada [39] 2003 R219K, I883M Janpanese 273/137 NA/NA NA/NA ≥50% stenosis CAD CAD- HB Probe Y Tan [40] 2003 I883M Chinese, Malays, Indians 616/640 58.4/45.1 100/100 ≥50% stenosis CAD Healthy PB RFLP Y Cenarro [41] 2003 R219K Spanish 216/158 53.3/67.9 66.7/41.8 NA CHD CHD- HB RFLP Y Evans [42] 2003 R219K German 114/629 55.5/43.4 71.1/53.3 NA CHD CHD- HB Probe Y Brousseau [43] 2001 R219K, I883M American 1014/1013 64.0/53.0 100/100 ≥50% stenosis CHD CHD- PB Probe Y NA: not available; MI: myocardial infarction; CAD: coronary artery disease; IHD: ischemic heart disease; RFLP: restriction fragment length polymorphisms; Y: yes; N: no; PB: population based; HB: hospital based; WHO: world health organization. Login to comment 80 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Association of R219K variant with CHD Significant heterogeneity was present among the 27 studies of the R219K polymorphism (Pb0.05). Login to comment 86 ABCA1 p.Arg219Lys However, significantly decreased CHD risk was found in two studies [38,41] conducted in familial hypercholesterolaemia (FH) subjects [K allele: OR=0.66, 95% CI: 0.51-0.87; dominant model: OR=0.57, 95% CI: 0.41-0.80; recessive model: OR=0.72, 95% CI: Fig. 2. Forest plot (random-effects model) of CHD associated with ABCA1 R219K polymorphism using dominant genetic model. Login to comment 91 ABCA1 p.Arg219Lys Table 2 Results of meta-analysis for ABCA1 R219K polymorphism and CHD risk. Sub-group analysis No. Login to comment 97 ABCA1 p.Ile883Met Subtotal (I-squared = 0.0%, p = 0.697) Frikke-Schmidt(Prospective) (2008) Tan (2003) Tregouet (2004) Other Caucasian Study Andrikovics (2006) 1.09 (0.98, 1.21) 0.98 (0.64, 1.51) 1.80 (0.94, 3.43) 1.03 (0.56, 1.89) ratio (95% CI) 0.79 (0.57, 1.10) 1.30 (0.76, 2.23) 1.31 (1.07, 1.61) 1.31 (1.04, 1.64) 1.08 (0.94, 1.24) 1.61 (0.81, 3.19) 0.89 (0.72, 1.11) 0.88 (0.42, 1.86) 1.14 (0.97, 1.33) 1.04 (0.60, 1.80) 1.11 (0.86, 1.44) 1.18 (1.02, 1.37) 1.04 (0.60, 1.80) 0.84 (0.66, 1.06) odds 0.35 (0.04, 3.19) 100.00 4.80 2.47 2.74 Weight 7.02 3.40 11.74 10.55 81.65 2.23 10.98 1.92 13.87 3.26 15.09 14.51 3.26 10.27 % 0.24 1.09 (0.98, 1.21) 0.98 (0.64, 1.51) 1.80 (0.94, 3.43) 1.03 (0.56, 1.89) ratio (95% CI) 0.79 (0.57, 1.10) 1.30 (0.76, 2.23) 1.31 (1.07, 1.61) 1.31 (1.04, 1.64) 1.08 (0.94, 1.24) 1.61 (0.81, 3.19) 0.89 (0.72, 1.11) 0.88 (0.42, 1.86) 1.14 (0.97, 1.33) 1.04 (0.60, 1.80) 1.11 (0.86, 1.44) 1.18 (1.02, 1.37) 1.04 (0.60, 1.80) 0.84 (0.66, 1.06) odds 0.35 (0.04, 3.19) 100.00 4.80 2.47 2.74 Weight 7.02 3.40 11.74 10.55 81.65 2.23 10.98 1.92 13.87 3.26 15.09 14.51 3.26 10.27 % 0.24 1 .2 1 5 Fig. 3. Forest plot (random-effects model) of CHD risk associated with ABCA1 I883M polymorphism using dominant genetic model. Login to comment 100 ABCA1 p.Arg219Lys No heterogeneity was present among the 7 studies of the R219K polymorphism (PN0.05 for all comparison). Login to comment 102 ABCA1 p.Ile883Met Association of I883M variant with CHD Overall, the per-allele OR of the 883I variant for CHD was 1.08 (95% CI: 0.96-1.21), with corresponding results under dominant and recessive genetic models of 1.09 (95% CI: 0.98-1.21; Fig. 3) and 1.19 (95% CI: 0.95-1.48), respectively. Login to comment 104 ABCA1 p.Ile883Met In the stratified analysis by ethnicity, source of controls, genotyping methods, sample size and HWE status, no significant associations between the I883M polymorphism and CHD risk were detected in almost all genetic models (Table 3). Login to comment 113 ABCA1 p.Ile883Met Table 3 Results of meta-analysis for ABCA1 I883M polymorphism and CHD risk. Sub-group analysis No. Login to comment 121 ABCA1 p.Arg219Lys Our results demonstrated that the K allele of the R219K polymorphism of ABCA1 is a protective factor for developing CHD. Login to comment 123 ABCA1 p.Ile883Met In addition, we failed to detect any positive relationship between CHD and I883M polymorphism of the ABCA1 gene. Login to comment 125 ABCA1 p.Arg219Lys In the stratified analysis by ethnicity, significant associations were found in East Asians and other population for R219K polymorphism in all genetic models; while no associations were detected among Caucasians for the polymorphism. Login to comment 132 ABCA1 p.Arg219Lys When analyses were restricted to FH subjects, the K allele of R219K polymorphism has a protective effect of CHD among Caucasian population. Login to comment 134 ABCA1 p.Arg219Lys Our results suggest that taking other loci than LDLR such as variant R219K of ABCA1 into consideration in CHD prediction would give a more reliable result for FH patients. Login to comment 140 ABCA1 p.Arg219Lys However, other studies failed to find an association between the R219K polymorphism and HDL [42,43,49]. Login to comment 148 ABCA1 p.Arg219Lys Despite these limitations, this meta-analysis suggests that ABCA1 R219K polymorphism was significantly associated with decreased risk of CHD, particularly in East Asian population. Login to comment 150 ABCA1 p.Ile883Met Funnel plot for the association between ABCA1 I883M status and CHD risk (Begg test, P=0.71); Egger's test was also performed to investigate the symmetry of the funnel plot (P=0.23). Login to comment 152 ABCA1 p.Ile883Met In addition, our meta-analysis did not support an association of the I883M of ABCA1 with CHD. Login to comment