Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response

• Autor(a) principal: Pulchinelli, Alvaro [UNIFESP]
• Data de Publicação: 2011
• Outros Autores: Costa, Ana Maria Massad [UNIFESP], Carvalho, Cristina Valletta de [UNIFESP], Nogueira-de-Souza, Naiara Corrêa [UNIFESP], Haidar, Mauro Abi [UNIFESP], Andriolo, Adagmar [UNIFESP], Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://repositorio.unifesp.br/handle/11600/34221; https://dx.doi.org/10.1186/1476-511X-10-197
• topic: Hepatic lipase gene; Menopause; Hormone replacement therapy; Lipid metabolism; SNP

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 (R) - 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.