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An association study of common SNPs in SREBP‐2 and SCAP genes with simvastatin response in Saudi patients
Author(s) -
Alzahrani Sarah,
AlNajai Mohammed,
AlMohanna Futwan,
Meyer Brian,
AlShaheed Mai,
Mohammed Gamal,
Pirmohamed Munir,
Dzimiri Nduna
Publication year - 2007
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.21.5.a182-c
Subject(s) - simvastatin , single nucleotide polymorphism , sterol regulatory element binding protein , medicine , cholesterol , genotype , endocrinology , allele , lipoprotein , statin , population , polymorphism (computer science) , gene , biology , sterol , genetics , environmental health
Several genes have been identified as potential modulators of statin response in hyperlipidaemia therapy. Sterol‐regulatory element binding protein (SREBP‐2) and cleavage‐activating protein (SCAP) are important regulatory genes in cholesterol synthesis. We investigated the role of these genes in statin response in the Saudi population. Plasma lipids and lipoproteins were measured before treatment and up to a year thereafter. Single nucleotide polymorphisms (SNPs) in the gene encoding SREBP‐2 C/G (rs4822063) and SCAP C/T (rs12487736) were genotyped in 116 hyperlipidaemic patients treated with 20 mg/day simvastatin for over 6 months, and 161 angiographed controls. Changes in lipid levels were estimated for each genotype and a linear regression model was used to examine the associations between SREBP‐2, SCAP and lipid levels. The mean change in triglycerides, cholesterol, low‐density lipoprotein and high density lipoprotein (HDL) were not significant in carriers of SREBP‐2 C /C and G/G, and SCAP C/C and T/T alleles. Interestingly, the mean increase in HDL was greater in C and T homozygotes when compared with C/T heterozygotes (10.8 ± 5.8 and 8.0 ± 6.4 [respectively] vs −2.2 ± 9.3, P = 0.030). Our data also indicates that the SCAP C/T polymorphism is a significant predictor of the HDL response to simvastatin therapy ( P = 0.014). In conclusion, our data suggest that the SCAP 58367 C/T gene polymorphism determines the effect on HDL level in patients on simvastatin. The clinical significance of this is unclear, and needs to be confirmed in a larger study group.