ABCMdb

PMID: 23372063

Villard EF, EI Khoury P, Frisdal E, Bruckert E, Clement K, Bonnefont-Rousselot D, Bittar R, Le Goff W, Guerin M
Genetic determination of plasma cholesterol efflux capacity is gender-specific and independent of HDL-cholesterol levels.
Arterioscler Thromb Vasc Biol. 2013 Apr;33(4):822-8. doi: 10.1161/ATVBAHA.112.300979. Epub 2013 Jan 31., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCA1 p.Arg219Lys The rs2230806 (ABCA1 p.R219K) SNP has been reported to be associated with HDL-C and the severity of atherosclerosis.12 The K219 allele is associated with higher plasma HDL-C and small HDL particle levels, and is proposed to be an antiatherogenic allele.13 The functional rs5082 (APOAII c.-265 T>C) SNP has been shown to be associated with coronary artery disease risk.14 Moreover, the rs1378577 (ABCG1 c.-134 T>G) SNP has been shown to modulate transcriptional activity of the human ABCG1 gene and was reported to be associated with plasma HDL-C levels in some studies, but not in others.15 The rs708272 (CETP TaqIB) SNP identified in the first intron of the CETP gene is associated with plasma CETP concentration, Received on: October 8, 2012; final version accepted on: January 10, 2013. Login to comment 10 ABCA1 p.Arg219Lys We demonstrated that rs17231506 (CETP c.- 1337 C>T), rs2230806 (ABCA1 p.R219K), rs1799837 (APOA1 c.-75 G>A), rs5086 (APOAII c.-265 T>C), and rs1800588 (LIPC c.-514 C>T) single nucleotide polymorphisms (SNPs) significantly modulate the capacity of whole-plasma to mediate cholesterol efflux from human macrophages in a sex-dependent manner. Login to comment 12 ABCA1 p.Arg219Lys In women, we identified the APOA1 c.-75 G>A and the LIPC c.-514 C>T variants as major contributors of interindividual variability of plasma efflux capacity, whereas the ABCA1 p.R219K and the APOAII c.-265 T>C SNPs mostly contribute to total variance of plasma efflux capacity in men. Login to comment 44 ABCA1 p.Arg219Lys Table 2.ߓ Impact of Genetic Variants on Overall Capacity of Plasma to Mediate Cholesterol Efflux From Human THP-1 Macrophages Additive Model Recessive or Dominant Model Model 1 Model 2 Model 1 Model 2 Mean Difference r2 P Valueߤ Mean Difference r2 P Valueߤ Mean Difference r2 P Valueߤ Mean Difference r2 P Valueߤ CETP TaqIB Women 1.2 ns 1.3 ns 0.7 ns 0.8 ns Men -0.9 ns -0.9 ns -2.9 ns -3.0 ns CETP c. -1337 C>T Women -0.9 ns -0.8 ns 0.8 ns 0.8 ns Men -2.6 ns -2.6 ns -8.9 1.01 0.03 -9.8 0.90 0.03 LIPC c. -514 C>T Women 4.0 1.50 0.02 4.1 1.47 0.03 9.9 2.08 0.004ߤ 10.4 2.06 0.003ߤ Men 0.8 ns 0.6 ns 3.4 ns 3.1 ns APOA1 c. -75 G>A Women 6.0 1.77 0.003ߤ 5.8 2.22 0.004ߤ 15.1 1.67 0.005ߤ 15.3 1.91 0.004ߤ Men -4.1 ns -4.0 ns -0.5 ns -0.8 ns ABCA1 p.R219K Women -0.9 ns -0.9 ns -2.5 ns -2.7 ns Men 4.3 1.22 0.002ߤ 4.5 1.18 0.002ߤ 13.2 2.39 0.001ߤ 13.6 2.38 0.001ߤ ABCG1 c. -134 T>G Women -2.6 ns -2.7 ns -6.0 ns -6.6 ns Men 2.2 ns 2.0 ns 3.4 ns 3.6 ns APOAII c. -265 T>C Women -0.4 ns -0.4 ns -0.1# ns -0.6# ns Men 4.8 1.41 0.01 4.6* 1.37 0.03 7.4# 1.93 0.005ߤ 7.4# 1.92 0.005ߤ For each SNP, 1 indicates the most frequent allele and 2 indicates the less frequent allele. Login to comment 82 ABCA1 p.Arg219Lys Multiple linear regression analyses including rs708272 (CETP TaqIB), rs17231506 (CETP c. -1337 C>T), rs1800588 (LIPC c. -514 C>T), rs1799837 (APOAI c. -75 G>A), rs2230806 (ABCA1 p.R219K), rs1378577 (ABCG1 c. -134 T>G), and rs5082 (APOAII c. -265 T>C) SNPs as predictive variables were performed to explain variance of plasma efflux capacity in men (left) and women (right). Login to comment