Kang Li1, Yanhong Liu1, Scott A Venners2, Yi-Hsiang Hsu3,4, Shanqun Jiang1,5, Justin Weinstock6, Yiyang Sun1, Binyan Wang5, Xiping Xu5,7. 1. 1 School of Life Sciences, Anhui University, Hefei, China. 2. 2 Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada. 3. 3 Institute for Aging Research, HSL and Harvard Medical School, Boston, MA, USA. 4. 4 Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA. 5. 5 Institute of Biomedicine, Anhui Medical University, Hefei, China. 6. 6 Department of Statistics, University of Virginia, Charlottesville, VA, USA. 7. 7 Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, IL, USA.
Abstract
OBJECTIVES: To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia. METHODS: We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: More patients in the good response group (27%) had LEPR Q223R than in the bad response group (16%, P = .046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPR Q223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline ( P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 ± 0.92, P = .036) and total cholesterol levels (change: -1.77 ± 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant. CONCLUSION: LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.
OBJECTIVES: To investigate whether LEPG2548A and LEPRQ223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia. METHODS: We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: More patients in the good response group (27%) had LEPRQ223R than in the bad response group (16%, P = .046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPRQ223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline ( P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 ± 0.92, P = .036) and total cholesterol levels (change: -1.77 ± 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant. CONCLUSION:LEPRQ223R polymorphism, but not LEPG2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.