title: Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response.
abstract: BACKGROUND
  Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX® - Amersham-Pharmacia, USA).
  
  
  RESULTS
  Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients.
  
  
  CONCLUSIONS
  The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.
authors: Laboratório de Biologia Molecular, Departamento de Ginecologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil. alvaro@alfa.epm.br
authors: Alvaro
authors: A
authors: Pulchinelli
authors: Ana Maria Massad
authors: AM
authors: Costa
authors: Cristina V
authors: CV
authors: de Carvalho
authors: Naiara Correa Nogueira
authors: NC
authors: de Souza
authors: Mauro A
authors: MA
authors: Haidar
authors: Adagmar
authors: A
authors: Andriolo
authors: Ismael D C Guerreiro
authors: ID
authors: da Silva
mesh_terms: D019943:Amino Acid Substitution; D000704:Analysis of Variance; D054316:Biomarkers, Pharmacological / Q000097:blood; D002784:Cholesterol / Q000097:blood; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007044:Hysterectomy; D008049:Lipase / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D054316:Biomarkers, Pharmacological; D004966:Estrogens, Conjugated (USP); D005819:Genetic Markers; C504173:LIPC protein, human; D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase