Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals

• Published in: Clinica chimica acta Vol. 389; no. 1-2; pp. 79 - 86
• Main Authors: Genvigir, Fabiana D.V., Soares, Sarah A., Hirata, Mario H., Willrich, Maria Alice V., Arazi, Simone S., Rebecchi, Ivanise M.M., Oliveira, Raquel, Bernik, Marcia M.S., Dorea, Egidio L., Bertolami, Marcelo C., Hirata, Rosario D.C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2008
• Subjects: ABCA1; Adult; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Base Sequence; Brazil; DNA Primers; Female; Humans; Linkage Disequilibrium; Lipids - blood; Male; Middle Aged; Pharmacogenetics; Plasma lipids; Polymorphism, Single Nucleotide; SNPs, Statins; ABCA1; Pharmacogenetics; SNPs, Statins; Plasma lipids
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2007.11.029

ABCA1 plays an important role in HDL metabolism. Single nucleotide polymorphisms (SNPs) in ABCA1 gene were associated with variation in plasma HDL-c. 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). The relation between ABCA1 SNPs and the lipid-lowering response to atorvastatin (10 mg/day/4 weeks) was also evaluated in 141 hypercholesterolemic (HC) individuals. The polymorphisms were detected by PCR-RFLP and confirmed by DNA sequencing. Linkage disequilibrium was found between the SNPs C-105T and C-14T in the HC group. HC individuals carrying -105CT/TT genotypes had higher serum HDL-c and lower triglyceride and VLDL-c concentrations as well as lower TG/HDL-c ratio compared to the -105CC carriers (p<0.05). The R219K SNP was associated with reduced serum triglyceride, VLDL-c and TG/HDL-c ratio in the HC group (p<0.05), and with an increased serum apoAI in NL individuals. The effects of ABCA1 SNPs on basal serum lipids of HC individuals were not modified by atorvastatin treatment. 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.