ABCMdb

PMID: 18164264

Genvigir FD, Soares SA, Hirata MH, Willrich MA, Arazi SS, Rebecchi IM, Oliveira R, Bernik MM, Dorea EL, Bertolami MC, Hirata RD
Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals.
Clin Chim Acta. 2008 Mar;389(1-2):79-86. Epub 2007 Dec 7., [PubMed]

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No. Mutations Sentence Comment

2 ABCA1 p.Arg219Lys Methods: The effect of the ABCA1 SNPs C-14T, R219K and of a novel variant C-105T on serum lipids was investigated in 367 unrelated Brazilian individuals (224 hypercholesterolemic and 143 normolipidemic). Login to comment 7 ABCA1 p.Arg219Lys The R219K SNP was associated with reduced serum triglyceride, VLDL-c and TG/HDL-c ratio in the HC group (pb0.05), and with an increased serum apoAI in NL individuals. Login to comment 9 ABCA1 p.Arg219Lys Conclusions: The ABCA1 SNPs R219K and C-105T were associated with a less atherogenic lipid profile but not with the lowering-cholesterol response to atorvastatin in a Brazilian population. Login to comment 25 ABCA1 p.Arg219Lys The R219K single nucleotide polymorphism (SNP) has been associated with protection against coronary artery disease (CAD) risk and severity [18-23]. Login to comment 65 ABCA1 p.Arg219Lys ABCA1 C-14T and R219K SNPs were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays. Login to comment 66 ABCA1 p.Arg219Lys The primers for C-14T (forward: 5'-CTCCACGTGCTTTCTGC- TGA-3', and reverse 5'-CACTCACTCTCGCTCGCAAT-3') and R219K (forward: 5'-GAAGAGATGATTCAACTTGGTGAC-3', and reverse 5'-GCCCAAAAG- TCTGAAAGAACAC-3') were selected using the ABCA1 reference sequence (GenBank Acession number AF275948) previously described [39]. Login to comment 68 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys The PCR thermal cycling conditions consisted of initial incubation at 98 °C for 3 min, followed by 29 cycles at 94 °C for 1 min, 57 °C for 2 min and 72 °C for 1 min for C-14T polymorphism or by 32 cycles at 94 °C for 45 s, 58 °C for 1.5 min and 72 °C for 1.5 min for R219K SNP and a final extension period of 72 °C for 10 min. Login to comment 70 ABCA1 p.Arg219Lys PCR products of C-14T and R219K SNPs (173 bp and 295 bp respectively) were analyzed by 1% agarose gel electrophoresis after ethidium bromide staining. Login to comment 71 ABCA1 p.Arg219Lys PCR products of the C-14T and R219K SNPs were initially digested with the MspI and StyI endonucleases (New England Biolabs Inc., Ipswich MA) respectively, at 37 °C. Login to comment 108 ABCA1 p.Arg219Lys Genotype and allele frequencies of ABCA1 R219K, C-14T and C-105T SNPs in NL and HC groups are shown in Table 2. Login to comment 109 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Table 2 Genotype and allele frequencies for ABCA1 R219K, C-14T and C-105T polymorphisms in the NL and HC groups Polymorphisms NL (143) HC (224) R219K genotypes, % RR 37.8 (54) 33.9 (76) χ2 =0.857 p=0.652 RK 43.3 (62) 48.2 (108) KK 18.9 (27) 17.9 (40) K allele 40.6 42.0 C-14T genotypes, % CC 42.0 (60) 43.3 (97) χ2 =2.000 p=0.363 CT 48.9 (70) 43.3 (97) TT 9.1 (13) 13.4 (30) T allele 33.6 35.0 C-105T genotypes, % CC 97.2 (139) 96.4 (216) Exact Fisher test p=1.000CT 2.8 (4) 3.1 (7) TT 0 (0) 0.5 (1) T allele 1.4 2.0 Number of individuals in parenthesis. Login to comment 110 ABCA1 p.Arg219Lys Hardy-Weinberg Equilibrium: R219K SNP: χ2 =0.76 (pN0.05). Login to comment 113 ABCA1 p.Arg219Lys Table 3 Effects of ABCA1 R219K polymorphism on basal serum lipids in NL and HC groups Variables NL genotypes (143) HC genotypes (224) 219RR (54) 219RK/ KK (89) p 219RR (76) 219RK/ KK (148) p Total cholesterol (mmol/l) 4.47±0.51 4.49±0.45 0.723 6.67±1.17 6.64±1.23 0.822 LDL-c (mmol/l) 2.59±0.48 2.55±0.44 0.696 4.39±1.11 4.41±1.13 0.890 HDL-c (mmol/l) 1.43±0.32 1.51±0.34 0.150 1.43±0.38 1.50±0.38 0.157 VLDL-c (mmol/l) 0.44±0.15 0.43±0.15 0.557 0.85±0.40 0.72±0.29 0.036 Triglyceride (mmol/l) 0.96±0.32 0.93±0.32 0.557 1.86±0.88 1.58±0.64 0.039 ApoAI (g/l) 1.36±0.29 1.46±0.27 0.035 1.37±0.28 1.40±0.30 0.513 ApoB (g/l) 0.88±0.24 0.84±0.21 0.416 1.31±0.33 1.31±0.28 0.876 ApoB/apoAI 0.67±0.23 0.60±0.21 0.074 1.00±0.33 0.99±0.37 0.732 TG/HDL-c 0.73±0.34 0.66±0.34 0.266 1.48±0.96 1.17±0.69 0.030 Number of individuals in parenthesis. Values are presented as mean±SD of log transformed data. Results were compared by t-test. ApoAI, apolipoprotein AI; apoB, apolipoprotein B; HC, hypercholesterolemic patients; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; NL, normolipidemic patients; TG, triglyceride; VLDL-c, very low-density lipoprotein cholesterol. Table 4 Effects of ABCA1 C-14T SNP on basal serum lipids in NL and HC groups Variables NL genotypes (143) HC genotypes (224) -14CC (60) -14CT/TT (83) p -14CC (97) -14CT/TT (127) p Total cholesterol (mmol/l) 4.45±0.39 4.51±0.52 0.739 6.68±1.29 6.63±1.14 0.778 LDL-c (mmol/l) 2.51±0.41 2.62±0.49 0.276 4.43±1.16 4.38±1.09 0.796 HDL-c (mmol/l) 1.53±0.34 1.45±0.34 0.262 1.50±0.41 1.45±0.36 0.466 VLDL-c (mmol/l) 0.44±0.15 0.44±0.15 0.922 0.75±0.36 0.78±0.31 0.138 Triglyceride (mmol/l) 0.94±0.33 0.95±0.32 0.922 1.62±0.79 1.71±0.69 0.151 ApoAI (g/l) 1.45±0.30 1.40±0.26 0.367 1.40±0.32 1.38±0.27 0.639 ApoB (g/l) 0.81±0.19 0.88±0.24 0.064 1.30±0.33 1.31±0.27 0.705 ApoB/apoAI 0.59±0.20 0.66±0.23 0.065 0.98±0.32 1.00±0.38 0.599 TG/HDL-c 0.67±0.36 0.70±0.33 0.500 1.23±0.85 1.31±0.77 0.147 Number of individuals in parenthesis. Values are presented as mean±SD of log transformed data. Results were compared by t-test. ApoAI, apolipoprotein AI; apoB, apolipoprotein B; HC, hypercholesterolemic patients; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; NL, normolipidemic patients; TG, triglyceride; VLDL-c, very low-density lipoprotein cholesterol. Login to comment 122 ABCA1 p.Arg219Lys These results are suggestive that ABCA1 R219K SNP and possibly the novel variant C-105T are associated with a less atherogenic serum lipid profile. Login to comment 128 ABCA1 p.Arg219Lys After the therapy, R219K and C-105T SNPs continued to show an association with a less atherogenic serum lipid profile (Fig. 2), but no ABCA1 SNP was associated with percentual variations in serum lipids after the treatment (data not shown). Login to comment 138 ABCA1 p.Arg219Lys In this study ABCA1 R219K SNP was associated with an increased serum apoAI in the NL group and with a reduced serum triglyceride and VLDL-c in HC individuals. Login to comment 153 ABCA1 p.Arg219Lys The C-105T SNP, like R219K also appears to be related to a less atherogenic lipid profile since the -105T allele was Fig. 2. Login to comment 155 ABCA1 p.Arg219Lys A) R219K SNP. Login to comment 179 ABCA1 p.Arg219Lys In our study, the HDL-c response to atorvastatin was independent of the ABCA1 C-105T, C-14T or R219K SNP. Login to comment 184 ABCA1 p.Arg219Lys In addition, R219K and, possibly, C-105T polymorphisms are associated with a less atherogenic serum lipid profile in Brazilian hypercholesterolemic patients before and after treatment with atorvastatin. Login to comment