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Effect of genetic polymorphisms in SREBF-SCAP pathway on therapeutic response to rosuvastatin in Saudi metabolic syndrome patients.

Department of Pharmacology, Faculty of Medicine, Rabigh Campus, King Abdulaziz University, Jeddah, Saudi Arabia. Department of Paediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. Department of Pharmacology, Faculty of Medicine, Rabigh Campus, King Abdulaziz University, Jeddah, Saudi Arabia & Faculty of Medicine, Ainshams University, Cairo, Egypt. Department of Laboratory Medicine, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Pharmacogenomics. 2018;(3):185-196
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Abstract

AIM: Genetic variants contribute to statins' therapeutic variability. SREBF-SCAP pathway is a key player in lipid homeostasis. Hence, effect of SREBF-SCAP polymorphisms on therapeutic response was studied. PATIENTS & METHODS Metabolic syndrome patients of either sex were prescribed rosuvastatin 10 mg for 24 weeks. Clinical, anthropometric and lipid measurements were done before and after treatment. Genotyping was done by pyrosequencing. RESULTS & CONCLUSION No associations of SCAP and SREBF-1a genotypes with baseline lipids but significant associations with lipid reductions were observed. Significant effect of SCAP (GG; B = -8.16, p = 0.001); SREBF-1a (GG; B = -7.47, p = 0.001) and SREBF-1a (-delG; B = -7.42, p = 0.001) was observed on total cholesterol reduction. Additive trend was found between SCAP genotypes and lipid reductions. A total of 88% responders have SCAP 'G' allele (p = 0.001). Patients carrying SCAP (GG) and SREBF-1a (GG and -delG) have 9.5-, 8.6- and 14.6-times more likelihood of being responders (p < 0.05). 'G' allele in SCAP and SREBF-1a is significant predictor of rosuvastatin response.

Methodological quality

Publication Type : Clinical Trial

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