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Liver X Receptor alpha Gene Polymorphisms and Simvastatin Therapy
Author(s) -
Alzahrani Sarah A.,
Dzimiri Nduna
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1134.4
Subject(s) - simvastatin , heterozygote advantage , medicine , endocrinology , genotype , single nucleotide polymorphism , cholesterol , alpha (finance) , liver x receptor , chemistry , gene , nuclear receptor , biochemistry , surgery , transcription factor , construct validity , patient satisfaction
Liver X receptor alpha subtype gene (LXRα) is involved in the regulation of cholesterol (Chol) metabolism and lipid biosynthesis, and may be downregulated by statins. The objective of this study was to investigate the prevalence and effect of two single nucleotide polymorphisms (SNPs), rs326220 and rs7934351, of the LXRα gene on patient responses to simvastatin therapy. Compared to 192 angiographic controls, the heterozygote C/T of the rs326220 was slight greater in patients (n =159) than in controls (5% vs 2.6%). Carriers of the homozygous C/C genotype in patients (151) exhibited greater reduction in total Chol (5.03 ± 0.11 pre vs 4.50 ± 0.10 post; p < 0.001) compared to the heterozygote C/T carriers (5.56 ± 0.37 vs 4.95 ± 0.44; p < 0.3) following 6 months treatment with 20mg/day simvastatin. Similar results were observed for low density lipoprotein (LDL) responses (p < 0.001 for C/C vs p < 0.07 for C/T). Interestingly, for the rs7934351, the homozygote A/A (2.5%) was present only in patients. The reduction in Chol (p < 0.001 vs p < 0.8) and LDL (p < 0.001 vs p < 0.9) was significantly greater in the heterozygote A/G (155) than in the A/A (4) carriers. Our results suggest that the heterozygote C/T of the rs326220 and homozygote A/A of the rs7934351are associated with lack of response to simvastatin therapy. Funding: The King Abdulaziz City for Science and Technology and King Faisal Specialist Hospital & Research Centre