title: Effects of LEP G2548A and LEPR Q223R Polymorphisms on Serum Lipids and Response to Simvastatin Treatment in Chinese Patients With Primary Hyperlipidemia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.
authors.affiliation: 1 School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: 1 School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2 Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Venners
authors.affiliation: 3 Institute for Aging Research, HSL and Harvard Medical School, Boston, MA, USA.|4 Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: 1 School of Life Sciences, Anhui University, Hefei, China.|5 Institute of Biomedicine, Anhui Medical University, Hefei, China.
authors.forename: Shanqun
authors.initials: S
authors.lastname: Jiang
authors.affiliation: 6 Department of Statistics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Weinstock
authors.affiliation: 1 School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 5 Institute of Biomedicine, Anhui Medical University, Hefei, China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: 5 Institute of Biomedicine, Anhui Medical University, Hefei, China.|7 Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, IL, USA.
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics / Q000627:therapeutic use*; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D054411:Receptors, Leptin; D019821:Simvastatin
keywords: LEP G2548A; LEPR Q223R; primary hyperlipidemia; simvastatin