ABCMdb

PMID: 17368464

Jensen MK, Pai JK, Mukamal KJ, Overvad K, Rimm EB
Common genetic variation in the ATP-binding cassette transporter A1, plasma lipids, and risk of coronary heart disease.
Atherosclerosis. 2007 Nov;195(1):e172-80. Epub 2007 Mar 26., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCA1 p.Ile883Met Three polymorphisms in the promoter region (-565C/T, -191G/C, and -17C/G) and two in the coding region (I883M and R1587K) were genotyped in the Nurses` Health Study. Login to comment 4 ABCA1 p.Ile883Met The I883M variant was associated with higher HDL-cholesterol levels among younger women. Login to comment 23 ABCA1 p.Arg219Lys Only the R1587K and the -565C/T promoter variant were found associated with apolipoprotein AI levels, the R219K SNP was associated with risk of myocardial infarction, and none of the 16 identified promoter SNPs were significantly associated with risk [7]. Login to comment 29 ABCA1 p.Ile883Met In total, three polymorphisms in the promoter: -565C/T (also referred to as -477C/T) [13,14], -191G/C (also known as C1176G) [17], and -17C/G (G1355C) [17], and two polymorphisms in the coding region: I883M in exon 18 (A2589G and I823M) [7,9], and R1587K in exon 35 [7] were genotyped in two well-characterized populations of female health professionals; the Nurses Health Studies I and II. Login to comment 50 ABCA1 p.Ile883Met Primers and probes used were designed by Applied Biosystems: -565C/T (rs2422493), -191G/C (rs1800976), -17C/G (rs2740483), I883M (rs4149313), and R1587K (rs2230808).Replicatequalitycontrolsampleswereincluded and genotyped with 100% concordance. Login to comment 84 ABCA1 p.Ile883Met Table 2 ABCA1 Genotype and allele distribution among cases and controls in the Nurses` Health Study I ABCA1 SNP n Cases (n = 249) n Controls (n = 494) B-allele frequency p* AA AB BB AA AB BB Cases Controls -565C/T 243 CC CT TT 484 CC CT TT T-allele frequency % 35 46 19 29 46 25 0.42 0.48 0.03 -191G/C 247 GG GC CC 492 GG GC CC C-allele frequency % 35 47 18 30 46 24 0.42 0.47 0.06 -17C/G 235 CC CG GG 477 CC CG GG G-allele frequency % 45 45 10 49 42 9 0.32 0.30 0.4 I883M 243 AA AG GG 482 AA AG GG M-allele frequency % 77 21 2 73 25 2 0.13 0.14 0.6 R1587K 246 GG GA AA 490 GG GA AA K-allele frequency % 58 37 5 56 38 6 0.23 0.25 0.6 Note: ABCA1 genotype frequencies in NHSII were as reported for NHSI controls. Login to comment 86 ABCA1 p.Ile883Met I883M: p = 0.004, and R1587K: p = 0.3). Login to comment 115 ABCA1 p.Ile883Met The I883M variant was associated with HDL-C concentrations among younger women, but not with CHD risk. Login to comment 118 ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met ABCA1 p.Ile883Met 0 ± 0.1 3.0 ± 0.1 GC 261 5.1 ± 0.1 1.0 ± 0.04 1.7 ± 0.02 2.8 ± 0.04 3.0 ± 0.0 CC 116 5.3 ± 0.1 1.0 ± 0.1 1.7 ± 0.03 3.1 ± 0.1 3.1 ± 0.1 p trend 0.9 0.4 0.2 0.5 0.4 -17C/G CC 267 5.2 ± 0.1 1.0 ± 0.04 1.7 ± 0.03 2.9 ± 0.04 3.0 ± 0.0 CG 236 5.1 ± 0.1 1.0 ± 0.04 1.7 ± 0.02 2.9 ± 0.1 3.1 ± 0.1 GG 51 5.3 ± 0.1 1.0 ± 0.1 1.8 ± 0.1 2.9 ± 0.1 2.9 ± 0.1 p trend 0.7 0.6 0.9 0.6 0.8 I883M AA 401 5.1 ± 0.04 1.0 ± 0.03 1.7 ± 0.02 2.9 ± 0.04 3.1 ± 0.0 AG 140 5.1 ± 0.1 1.0 ± 0.1 1.8 ± 0.04 2.7 ± 0.1 2.9 ± 0.1 GG 13 5.4 ± 0.2 1.1 ± 0.2 1.9 ± 0.1 2.9 ± 0.1 2.9 ± 0.1 p trend 0.8 0.6 <0.01 <0.01 0.02 R1587K GG 310 5.2 ± 0.1 1.0 ± 0.04 1.7 ± 0.02 2.9 ± 0.04 3.1 ± 0.0 GA 211 5.1 ± 0.1 1.0 ± 0.04 1.8 ± 0.03 2.8 ± 0.05 3.0 ± 0.1 AA 35 5.1 ± 0.1 0.8 ± 0.08 1.7 ± 0.1 2.8 ± 0.1 3.0 ± 0.1 p trend 0.2 0.01 0.4 0.1 0.1 Women ≥55 years of age -565C/T CC 105 5.8 ± 0.3 1.5 ± 0.1 1.5 ± 0.03 3.4 ± 0.1 3.9 ± 0.2 CT 173 7.0 ± 1.1 1.4 ± 0.06 1.6 ± 0.03 3.4 ± 0.1 4.6 ± 0.6 TT 100 6.4 ± 0.4 1.6 ± 0.1 1.5 ± 0.04 3.6 ± 0.1 4.4 ± 0.3 p trend 0.2 0.8 0.9 0.1 0.1 -191G/C GG 110 5.8 ± 0.3 1.5 ± 0.1 1.5 ± 0.03 3.5 ± 0.1 3.9 ± 0.1 GC 176 6.9 ± 1.0 1.4 ± 0.1 1.6 ± 0.03 3.4 ± 0.1 4.6 ± 0.6 CC 110 6.4 ± 0.4 1.6 ± 0.1 1.5 ± 0.04 3.7 ± 0.1 4.5 ± 0.3 p trend 0.2 0.6 0.7 0.2 0.03 -17C/G CC 187 6.2 ± 0.3 1.5 ± 0.1 1.5 ± 0.03 3.6 ± 0.1 4.3 ± 0.2 CG 153 6.9 ± 1.1 1.4 ± 0.1 1.5 ± 0.03 3.3 ± 0.1 4.6 ± 0.6 GG 34 5.7 ± 0.7 1.6 ± 0.1 1.6 ± 0.1 3.7 ± 0.2 4.3 ± 0.5 p trend 0.7 0.9 0.3 0.3 0.2 I883M AA 275 5.9 ± 0.1 1.5 ± 0.1 1.6 ± 0.03 3.4 ± 0.1 4.0 ± 0.1 AG 96 8.1 ± 2.0 1.5 ± 0.1 1.5 ± 0.04 3.6 ± 0.1 5.3 ± 1.1 GG 5 6.3 ± 0.4 3.0 ± 0.6 1.2 ± 0.1 3.6 ± 0.2 4.7 ± 0.4 p trend 0.3 0.3 0.1 0.1 0.3 R1587K GG 215 5.7 ± 0.2 1.5 ± 0.1 1.6 ± 0.02 3.4 ± 0.1 3.9 ± 0.1 GA 144 7.8 ± 1.7 1.5 ± 0.1 1.5 ± 0.03 3.5 ± 0.1 5.1 ± 0.9 AA 23 6.1 ± 0.5 1.6 ± 0.1 1.4 ± 0.1 3.6 ± 0.2 4.3 ± 0.3 p trend 0.2 0.9 0.4 0.6 0.2 Linear regression analyses were adjusted for age, smoking, BMI, alcohol intake, history of hypertension, parental history of CHD before age 60, diabetes at baseline, menopausal status and PMH. Login to comment 121 ABCA1 p.Ile883Met Table 4 Odds ratios [OR] and 95% confidence intervals [CI] of coronary heart disease according to ABCA1 genotype in the Nurses` Health Study I SNP/inheritance Indicator Recessive Dominant Codominant AA AB BB AA/AB BB AA AB/BB Per B-allele -565C/T CC CT TT CC/CT TT CC CT/TT Cases/controls 86/142 112/222 45/120 198/364 45/120 86/142 157/342 OR (95% CI)a 1 0.8 (0.6-1.2) 0.6 (0.4-0.9) 1 0.7 (0.5-1.0) 1 0.7 (0.5-1.0) 0.8 (0.6-1.0) OR (95% CI)b 1 0.7 (0.5-1.1) 0.6 (0.4-0.9) 1 0.7 (0.5-1.1) 1 0.7 (0.5-1.0) 0.8 (0.6-1.0) -191G/C GG GC CC GG/GC CC GG GC/CC Cases/controls 87/150 115/224 45/118 202/374 45/118 87/150 160/342 OR (95% CI)a 1 0.9 (0.6-1.2) 0.6 (0.4-1.0) 1 0.7 (0.5-1.0) 1 0.8 (0.6-1.1) 0.8 (0.7-1.0) OR (95% CI)b 1 0.8 (0.5-1.1) 0.6 (0.4-1.0) 1 0.7 (0.5-1.1) 1 0.7 (0.5-1.0) 0.8 (0.6-1.0) -17C/G CC CG GG CC/CG GG CC CG/GG Cases/controls 106/233 106/200 23/44 212/433 23/44 106/233 129/244 OR (95% CI)a 1 1.2 (0.9-1.7) 1.1 (0.6-2.0) 1 1.0 (0.6-1.8) 1 1.2 (0.9-1.6) 1.1 (0.9-1.4) OR (95% CI)b 1 1.1 (0.7-1.5) 1.3 (0.7-2.4) 1 1.3 (0.7-2.3) 1 1.1 (0.8-1.6) 1.1 (0.9-1.5) I883M AA AG GG AA/AG GG AA AG/GG Cases/controls 184/353 54/121 5/8 238/474 5/8 184/353 59/129 OR (95% CI)a 1 0.8 (0.6-1.2) 1.3 (0.4-4.1) 1 1.4 (0.4-4.2) 1 0.9 (0.6-1.3) 0.9 (0.7-1.3) OR (95% CI)b 1 0.9 (0.6-1.4) 1.2 (0.3-4.5) 1 1.2 (0.3-4.6) 1 0.9 (0.6-1.4) 1.0 (0.7-1.4) R1587K GG GA AA GG/GA AA GG GA/AA Cases/controls 144/275 90/188 12/27 234/463 12/27 144/275 102/215 OR (95% CI)a 1 0.9 (0.6-1.2) 0.8 (0.4-1.7) 1 0.9 (0.4-1.8) 1 0.9 (0.7-1.2) 0.9 (0.7-1.2) OR (95% CI)b 1 0.9 (0.7-1.3) 0.7 (0.3-1.5) 1 0.7 (0.3-1.5) 1 0.9 (0.6-1.4) 0.9 (0.7-1.2) a Logistic regression models adjusted for age, smoking, time of blood draw. Login to comment 135 ABCA1 p.Ile883Met ABCA1 p.Ile883Met Similarly discrepant results have been reported for other ABCA1 pro- Table 5 Pairwise linkage disequilibrium (D ) and correlation coefficient (r2) between ABCA1 polymorphisms Polymorphism Linkage disequilibrium (D ) -565C/T -191G/C -17C/G I883M R1587K Correlation coefficient (r2) -565C/T - 0.99 0.97 0.15 0.01 -191G/C 0.96 - 1.00 0.13 0.02 -17C/G 0.36 0.37 - 0.02 0.05 I883M 0.0 0.0 0.0 - 0.08 R1587K 0.0 0.0 0.0 0.0 - Note: Results presented from the Nurses` Health Study II (same estimates as among Nurses` Health Study I controls). Login to comment 166 ABCA1 p.Arg219Lys Moreover, we did not have information on the R219K SNP that has consistently been associated with lower CHD risk previously [7-9]. Login to comment