Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response
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2011-11-02
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Pulchinelli, Alvaro [UNIFESP]
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]
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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.
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Lipids in Health and Disease. London: Biomed Central Ltd, v. 10, 9 p., 2011.