ABCMdb

PMID: 22982414

Jiang M, Lv L, Wang H, Yang X, Ji H, Zhou F, Zhu W, Cai L, Gu X, Sun J, Dong Q
Meta-analysis on association between the ATP-binding cassette transporter A1 gene (ABCA1) and Alzheimer's disease.
Gene. 2012 Dec 1;510(2):147-53. doi: 10.1016/j.gene.2012.09.009. Epub 2012 Sep 13., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys 34 Conclusions: In summary, there was no significant association detected between ABCA1 R219K, I883M and 35 R1587K polymorphisms and risk for AD. Login to comment 28 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys In consideration of the extensive role of ABCA1 in the develop- 77 ment of AD, we carried out a comprehensive meta-analysis on all eligible 78 case-control studies to estimate the overall AD risk of ABCA1 R219K 79 (rs2230806), I883M (rs4149313) and R1587K (rs2230808) polymor- 80 phisms as well as to quantify the between-study heterogeneity and po- 81 tential bias. Login to comment 30 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys In consideration of the extensive role of ABCA1 in the development of AD, we carried out a comprehensive meta-analysis on all eligible case-control studies to estimate the overall AD risk of ABCA1 R219K (rs2230806), I883M (rs4149313) and R1587K (rs2230808) polymorphisms as well as to quantify the between-study heterogeneity and potential bias. Login to comment 63 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys For the R219K 155 polymorphism, 12 studies were available, including a total of 5372 156 cases and 5180 controls. For the I883M polymorphism, 5 studies in- 157 volved a total of 2118 cases and 1852 controls. For the R1587K poly- 158 morphism, 6 studies involved a total of 2942 cases and 2720 controls. Login to comment 65 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys For the R219K polymorphism, 12 studies were available, including a total of 5372 cases and 5180 controls. For the I883M polymorphism, 5 studies involved a total of 2118 cases and 1852 controls. For the R1587K polymorphism, 6 studies involved a total of 2942 cases and 2720 controls. Login to comment 68 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Association of R219K variant with AD 165 For AD risk and the R219K polymorphism of ABCA1, our meta- 166 analysis gave an overall OR of 1.03 (95% CI: 0.93-1.14; p=0.56) without 167 statistically significant between-study heterogeneity (Fig. 2). Login to comment 70 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Association of R219K variant with AD For AD risk and the R219K polymorphism of ABCA1, our meta-analysis gave an overall OR of 1.03 (95% CI: 0.93-1.14; p=0.56) without statistically significant between-study heterogeneity (Fig. 2). Login to comment 78 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 t1:3 Study Year Ethnicity Genotyping method No. of case/control Diagnostic criterion Outcome Mean age of onset Mean age of case/control Gender of case/control (% male) Polymorphism t1:4 Wollmer 2003 Swedish Pyrosequencing 169/166 NINCDS-ADRDA LOAD; EOAD 70.1 73.5/69.0 42.0/51.0 R219K t1:5 Li 2004 American RT-PCR 418/376 NINCDS-ADRDA LOAD 75.5 77.5/NA 43.0/44.0 R219K, I883M, R1587K t1:6 Katzov 2004 Swedish; English DASH 974/751 NINCDS-ADRDA LOAD; EOAD 70.8 76.6/75.4 40.2/44.1 R219K, I883M, R1587K t1:7 Shibata 2006 North American SNAPshot 218/195 NINCDS-ADRDA LOAD 75.0 NA/73.1 47.0/48.0 R219K, I883M, R1587K t1:8 Kölsch 2006 German RFLP 241/294 DSM IV LOAD; EOAD NA 73.2/71.8 28.5/45.6 R219K t1:9 Wahrle 2007 American MassArray 1225/1431 AD patients LOAD NA NA/NA NA/NA R219K t1:10 Chu 2007 Chinese MassArray 272/278 NINCDS-ADRDA LOAD NA 78.0/72.0 51.0/70.1 R219K, I883M, R1587K t1:11 Wang 2007 Chinese RFLP 168/215 NINCDS-ADRDA LOAD; EOAD 69.3 73.5/72.3 46.0/41.4 R219K t1:12 Sundar 2007 American Pyrosequencing 992/699 NINCDS-ADRDA LOAD 72.3 NA/75.3 34.0/38.0 R219K t1:13 Rodríguez-Rodríguez 2007 Spainish TaqMan 371/436 NINCDS-ADRDA LOAD 72.3 75.8/80.8 34.0/31.0 R219K, I883M, R1587K t1:14 Li 2008 Canadian Affymetrix genechip 691/682 DSM IV LOAD 80.2 NA/NA 100/100 R1587K t1:15 Khorshid 2010 Iranian RFLP 154/162 DSM IV LOAD NA 78.5/77.1 40.9/38.9 R219K t1:16 Sun 2012 Chinese RFLP 321/349 DSM IV LOAD; EOAD NA 70.0/68.5 38.0/35.8 R219K t1:17 NA: Not available, DASH: Dynamic Allele Specific Hybridization, LOAD: Late-onset Alzheimer disease, EOAD: Early-onset Alzheimer disease, DSM-IV: Diagnostic and Statistical Manual of t1:18 Mental Disorders IV. Login to comment 79 ABCA1 p.Arg219Lys Fig. 2. Forest plot from the meta-analysis of Alzheimer's disease risk and ABCA1 R219K polymorphism (K versus R). Login to comment 80 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 3 182 The data on genotypes of the R219K polymorphism among cases 183 and controls stratified by APOE ε4-allele status were available in 5 184 (including 2131 cases and 2343 controls) studies. Login to comment 81 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Using the dominant 185 genetic model, the APOE ε4-allele carrier with the risk allele of R219K 186 variant had no significantly increased AD risk compared to APOE 187 ε4-allele non-carrier with an OR of 1.04 [95% CI: 0.83-1.31; P(Z)= 188 0.73; P(Q)=0.26]. Login to comment 82 ABCA1 p.Arg219Lys The data on genotypes of the R219K polymorphism among cases and controls stratified by APOE b5;4-allele status were available in 5 (including 2131 cases and 2343 controls) studies. Login to comment 83 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Association of I883M variant with AD 190 Overall, the per-allele OR of the 883M variant for AD was 1.10 191 (95% CI: 0.96-1.26; p=0.16; Fig. 3), with corresponding results for 192 heterozygous and homozygous of 1.12 (95% CI: 0.94-1.33; p=0.22) 193 and 1.21 (95% CI: 0.80-1.82; p=0.89), respectively. In the stratified 194 analysis by ethnicity and sample size, no significant associations be- 195 tween the I883M polymorphism and AD risk were detected in all ge- 196 netic models (Table 3). Login to comment 85 ABCA1 p.Ile883Met ABCA1 p.Ile883Met Association of I883M variant with AD Overall, the per-allele OR of the 883M variant for AD was 1.10 (95% CI: 0.96-1.26; p=0.16; Fig. 3), with corresponding results for heterozygous and homozygous of 1.12 (95% CI: 0.94-1.33; p=0.22) and 1.21 (95% CI: 0.80-1.82; p=0.89), respectively. In the stratified analysis by ethnicity and sample size, no significant associations between the I883M polymorphism and AD risk were detected in all genetic models (Table 3). Login to comment 86 ABCA1 p.Arg219Lys Table 2 t2:1 t2:2 Main results of pooled ORs with CI for association of the R219K polymorphism and Alzheimer's disease risk in the meta-analysis. Login to comment 87 ABCA1 p.Ile883Met t2:3 Sub-group analysis No. of data sets No. of case/control K allele Heterozygous Homozygous t2:4 OR (95% CI) P (Z) P (Q) I2 (%) OR (95% CI) P (Z) P (Q) I2 (%) OR (95% CI) P (Z) P (Q) I2 (%) t2:5 Total 15 5372/5180 1.03 (0.93-1.14) 0.56 0.01 23 1.07 (0.98-1.17) 0.12 0.43 10 0.95 (0.77-1.17) 0.62 0.06 21 t2:6 Ethnicity t2:7 Caucasian 11 4897/4669 1.04 (0.96-1.14) 0.32 0.18 14 1.09 (1.00-1.19) 0.06 0.64 0 1.02 (0.83-1.25) 0.87 0.18 19 t2:8 Asian 4 475/511 0.91 (0.72-1.16) 0.76 0.05 21 0.91 (0.61-1.36) 0.66 0.15 8 0.71 (0.38-1.30) 0.26 0.09 26 t2:9 Onset type t2:10 EOAD 2 244/293 1.06 (0.82-1.36) 0.68 0.55 5 1.16 (0.81-1.67) 0.42 0.93 0 1.02 (0.56-1.85) 0.95 0.53 0 t2:11 LOAD 10 3340/2785 1.06 (0.96-1.17) 0.27 0.19 16 1.14 (1.00-1.31) 0.06 0.51 12 0.99 (0.78-1.27) 0.94 0.15 17 t2:12 Mixed 4 1788/2102 0.92 (0.76-1.10) 0.35 0.06 33 0.92 (0.74-1.14) 0.44 0.17 19 0.85 (0.57-1.27) 0.43 0.07 22 t2:13 APOE status t2:14 ε4 carriers 5 1099/552 1.09 (0.93-1.28) 0.30 0.59 0 1.37 (0.96-1.96) 0.08 0.90 0 0.96 (0.66-1.40) 0.84 0.66 0 t2:15 ε4 non-carriers 5 1032/1791 0.97 (0.79-1.20) 0.80 0.07 24 1.07 (0.77-1.50) 0.67 0.04 57 0.88 (0.61-1.27) 0.49 0.13 18 t2:16 Sample size t2:17 b300 8 1334/1608 0.98 (0.85-1.14) 0.82 0.10 13 1.00 (0.85-1.18) 0.97 0.37 2 0.93 (0.67-1.29) 0.66 0.16 6 t2:18 ≥300 7 4038/3572 1.03 (0.91-1.17) 0.61 0.05 42 1.10 (1.00-1.22) 0.06 0.45 0 0.96 (0.71-1.30) 0.80 0.05 39 Fig. 3. Forest plot from the meta-analysis of Alzheimer's disease risk and ABCA1 I883M polymorphism (M versus I). Login to comment 88 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys Table 2 Main results of pooled ORs with CI for association of the R219K polymorphism and Alzheimer's disease risk in the meta-analysis. Sub-group analysis No. of data sets No. of case/control K allele Heterozygous Homozygous OR (95% CI) P (Z) P (Q) I2 (%) OR (95% CI) P (Z) P (Q) I2 (%) OR (95% CI) P (Z) P (Q) I2 (%) Total 15 5372/5180 1.03 (0.93-1.14) 0.56 0.01 23 1.07 (0.98-1.17) 0.12 0.43 10 0.95 (0.77-1.17) 0.62 0.06 21 Ethnicity Caucasian 11 4897/4669 1.04 (0.96-1.14) 0.32 0.18 14 1.09 (1.00-1.19) 0.06 0.64 0 1.02 (0.83-1.25) 0.87 0.18 19 Asian 4 475/511 0.91 (0.72-1.16) 0.76 0.05 21 0.91 (0.61-1.36) 0.66 0.15 8 0.71 (0.38-1.30) 0.26 0.09 26 Onset type EOAD 2 244/293 1.06 (0.82-1.36) 0.68 0.55 5 1.16 (0.81-1.67) 0.42 0.93 0 1.02 (0.56-1.85) 0.95 0.53 0 LOAD 10 3340/2785 1.06 (0.96-1.17) 0.27 0.19 16 1.14 (1.00-1.31) 0.06 0.51 12 0.99 (0.78-1.27) 0.94 0.15 17 Mixed 4 1788/2102 0.92 (0.76-1.10) 0.35 0.06 33 0.92 (0.74-1.14) 0.44 0.17 19 0.85 (0.57-1.27) 0.43 0.07 22 APOE status b5;4 carriers 5 1099/552 1.09 (0.93-1.28) 0.30 0.59 0 1.37 (0.96-1.96) 0.08 0.90 0 0.96 (0.66-1.40) 0.84 0.66 0 b5;4 non-carriers 5 1032/1791 0.97 (0.79-1.20) 0.80 0.07 24 1.07 (0.77-1.50) 0.67 0.04 57 0.88 (0.61-1.27) 0.49 0.13 18 Sample size b300 8 1334/1608 0.98 (0.85-1.14) 0.82 0.10 13 1.00 (0.85-1.18) 0.97 0.37 2 0.93 (0.67-1.29) 0.66 0.16 6 ࣙ300 7 4038/3572 1.03 (0.91-1.17) 0.61 0.05 42 1.10 (1.00-1.22) 0.06 0.45 0 0.96 (0.71-1.30) 0.80 0.05 39 Fig. 3. Forest plot from the meta-analysis of Alzheimer's disease risk and ABCA1 I883M polymorphism (M versus I). Login to comment 92 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys The statistical results still did not show publi- 210 cation bias in these studies for R219K (Begg test, P=0.67; Egger test, 211 P=0.83; Supplementary Fig. 4), I883M (Begg test, P=0.42; Egger 212 test, P=0.62; Supplementary Fig. 5) and R1587K (Begg test, P= 213 0.13; Egger test, P=0.49; Supplementary Fig. 6). Login to comment 104 ABCA1 p.Ile883Met ABCA1 p.Ile883Met Second, many previous studies have shown that high Table 3 t3:1 t3:2 Main results of pooled ORs with CI for association of the I883M polymorphism and Alzheimer's disease risk in the meta-analysis. Login to comment 113 ABCA1 p.Arg219Lys This may indicate that the R219K genotype has a minor effect on AD than that of the APOE b5;4b5;4 genotype. Login to comment 114 ABCA1 p.Arg219Lys This may indicate that the R219K genotype has 254 a minor effect on AD than that of the APOE ε4ε4 genotype. Login to comment 121 ABCA1 p.Ile883Met Finally, studies investigating I883M and R1587K are currently limited. Login to comment 122 ABCA1 p.Ile883Met Finally, 274 studies investigating I883M and R1587K are currently limited. Login to comment 126 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys To conclude, this meta-analysis suggests that the R219K, I883M and R1587K polymorphisms of ABCA1 are not associated with AD susceptibility. Login to comment 127 ABCA1 p.Ile883Met ABCA1 p.Arg219Lys 282 To conclude, this meta-analysis suggests that the R219K, I883M 283 and R1587K polymorphisms of ABCA1 are not associated with AD 284 susceptibility. Login to comment