ABCMdb

PMID: 20346718

Tsai MY, Ordovas JM, Li N, Straka RJ, Hanson NQ, Arends VL, Arnett D
Effect of fenofibrate therapy and ABCA1 polymorphisms on high-density lipoprotein subclasses in the Genetics of Lipid Lowering Drugs and Diet Network.
Mol Genet Metab. 2010 Jun;100(2):118-22. Epub 2010 Mar 6., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCA1 p.Arg219Lys However, after fenofibrate treatment the KK genotype of R1587K (mean 4.40 lmol/L; p = 0.004) and the RK genotype of R219K (mean 1.60 lmol/L; p = 0.02) polymorphisms were associated with significantly increased small HDL. Login to comment 7 ABCA1 p.Arg219Lys The R1587K KK genotype (mean 4.80 lmol/L; p = 0.0002) and the R219K KK genotype (mean 2.50 lmol/L; p = 0.02) were also associated with increased HDL particle concentrations. Login to comment 22 ABCA1 p.Arg219Lys Molecular Genetics and Metabolism 100 (2010) 118-122 Contents lists available at ScienceDirect Molecular Genetics and Metabolism journal homepage: www.elsevier.com/locate/ymgme on HDL-C concentration; specifically, the K allele of the ABCA1 R219K polymorphism has been associated with increased HDL-C concentration [8-11] and a reduced incidence of coronary artery disease (CAD) events [8,9]. Login to comment 23 ABCA1 p.Arg219Lys In a subcohort of the Multi-Ethnic Study of Atherosclerosis (MESA) we demonstrated that the K allele of the R219K polymorphism (designated as the 1051 A allele in MESA) is associated with both a lower prevalence of coronary artery calcium even when adjusted for HDL-C [12] and increased small HDL particle concentration [13]. Login to comment 47 ABCA1 p.Arg219Lys The ABCA1 rs2297404, rs2578575, rs4149272, and rs2230806 (R219K) polymorphisms were genotyped by Applied Biosystems TaqMan SNP system. Login to comment 68 ABCA1 p.Arg219Lys Table 3 shows that quantitative changes in HDL subclass particle concentrations from baseline to after fenofibrate treatment are significant for the ABCA1 R1587K and R219K polymorphisms. Login to comment 70 ABCA1 p.Arg219Lys The R219K RK (p = 0.02) genotype was associated with 1.6-fold higher small HDL, compared to the RR genotype. Login to comment 71 ABCA1 p.Arg219Lys In addition, HDL particle concentration was 2.5-fold higher in the KK genotype of the R219K polymorphism, compared to the RR genotype (p = 0.02). Login to comment 79 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Table 2 Differences in HDL subclass particle concentrations between genotypes of ABCA1 polymorphisms, as compared to reference genotypes, at baseline (pre-fenofibrate treatment) in 287 GOLDN participants. Polymorphism (reference genotype) na Comparison genotype n Small HDL (lmol/L) Medium HDL (lmol/L)c Large HDL (lmol/L) HDL particles (lmol/L) HDL size (nm) Mean (lower 95% CI, upper 95% CI)b Mean (lower 95% CI, upper 95% CI) Mean (lower 95% CI, upper 95% CI) Mean (lower 95% CI, upper 95% CI) Mean (lower 95% CI, upper 95% CI) R1587K (RR) 152 RK 84 1.00 (À0.50, 2.60) À0.04 (À0.74, 0.67) À0.29 (À1.00, 0.46) 0.32 (À1.30, 2.00) 0.03 (À0.07, 0.12) KK 14 À0.53 (À3.70, 2.70) À0.72 (À2.20, 0.74 0-0.67 (À2.20, 0.89) À2.50 (À5.80, 0.89) À0.02 (À0.22, 0.18) R219K (RR) 155 RK 113 À0.10 (À1.70, 1.50) À0.04 (À0.77, 0.68) 0.00 (À0.77, 0.78) 0.50 (À1.10, 2.10) À0.01 (À0.11, 0.09) KK 19 À0.01 (À2.90, 2.80) À0.82 (À2.10, 0.48) 0.41 (À0.98, 1.80) 0.47 (À2.50, 3.40) À0.05 (À0.23, 0.13) M883I (II) 191 IM 57 À0.28 (À1.90, 1.40) À0.06 (À0.82, 0.70) À0.05 (À0.85, 0.75) À0.32 (À2.10, 1.4) À0.03 (À0.13, 0.08) MM 1 9.50 (À1.70, 21.00) À2.50 (À7.60, 2.60) À0.09 (À5.50, 5.30) 9.30 (À2.40, 21.00) 0.02 (À0.68, 0.720 rs4149272 (GG) 128 GA 128 0.15 (À7.70, 8.00) À2.10 (À5.70, 1.50) 1.60 (À2.20, 5.50) 0.58 (À7.60, 8.80) 0.01 (À0.48, 0.50) AA 31 À7.90 (À22.00, 5.90) 2.40 (À3.90, 8.70) 3.70 (À3.00, 10.00) À1.60 (À16.00, 13.00) 0.47 (À0.39, 1.30) rs2297404 (GG) 252 GC 34 1.80 (À0.49, 4.10) À0.36 (À1.40, 0.68) À0.31 (À1.40, 0.81) 1.60 (À0.70, 3.90) À0.16 (À0.31, À0.02)d CC 1 À1.50 (À12.00, 9.50) 2.10 (À2.90, 7.10) 1.40 (À4.00, 6.70) 0.77 (À11.00, 12.00) 0.06 (À0.63, 0.75) rs2575875 (GG) 126 GA 129 0.24 (À7.70, 8.20) 1.90 (À1.70, 5.60) À2.10 (À6.00, 1.80) À1.30 (À9.60, 7.00) À0.05 (À0.55, 0.44) AA 32 8.60 (À5.10, 22.00) À2.60 (À8.90, 3.60) À5.10 (À12.00, 1.60) 0.23 (À14.00, 15.00) À0.67 (À1.50, 0.19) a Total genotypes for R1587K and M883I do not add to 287 because genotypes of 37 participants could not be determined for R1587K and 38 for M883I. Login to comment 86 ABCA1 p.Arg219Lys In accordance with this observation, our laboratory demonstrated that the KK genotype of the R219K polymorphism of ABCA1 was associated with an increase in small HDL particles [13]; the finding suggests that the KK genotype is associated with increased ABCA1 activity, resulting in increased cholesterol efflux. Login to comment 93 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys While we previously demonstrated that the ABCA1 1051 A allele (aka R219K K allele) was associated with increased small HDL in the MESA population [13], in the current study there was no increase in small HDL subclass when stratified by ABCA1 R219K genotype. Login to comment 94 ABCA1 p.Arg219Lys Rather, we show that the K alleles of R219K and R1587K are associated 1.6- and 4.4-fold increases in small HDL after fenofibrate treatment. Login to comment 98 ABCA1 p.Arg219Lys Finally, to expand on previous work that examined the ABCA1 polymorphism R219K, five additional SNPs were examined in the current study-of these, R1587K was found to have a significant effect on small HDL concentration (p = 0.004). Login to comment