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

Haidar, De, Pulchinelli Alvaro, Massad, Andriolo Adagmar, Guerreiro

Description

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.

Sujets

• Ménopause
• Hormone replacement therapy
• Lipid metabolism
• SNP

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 10
• Langue: English

Extrait

Pulchinelliet al.Lipids in Health and Disease2011,10:197 http://www.lipidworld.com/content/10/1/197

R E S E A R C HOpen Access Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response 1* 11 1 Alvaro Pulchinelli Jr, Ana Maria Massad Costa , Cristina V de Carvalho , Naiara Correa Nogueira de Souza , 2 31 Mauro A Haidar , Adagmar Andrioloand Ismael DC Guerreiro da Silva

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. Keywords: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. Although also expressed in other tissues, over 95% per cent of the total HL activity is found in the liver [1]. As a key enzyme in lipoprotein metabolism, HL hydrolyzes triglycerides (TG), intermediatedensity lipoprotein (IDLC), highdensity lipoprotein (HDLC), and the sur face phospholipids and core TG of small verylowden sity lipoprotein (VLDLC) remnants. HL also aids in the binding of lipoproteins to cellular receptors. In vitro

* Correspondence: [e-mail] 1 Laboratório de Biologia Molecular, Departamento de Ginecologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil Full list of author information is available at the end of the article

studies have demonstrated that HL facilitates the bind ing and entrance of chylomicrons, chylomicron rem nants, VLDLcholesterol (VLDLC), LDLC [2,3] and HDL cholesterol (HDLC) [46] into a number of differ ent cell types. Fertile females have lower HL activity than males [7,8]. Patients with HL deficiency often present with hypercholesterolemia, hypertriglyceridemia and increased levels of VLDLC, remnant chylomicrons, IDLC, TGrich LDLC, and HDLC [911]. However, because not all patients with HL deficiency show these metabolic changes, the condition is sometimes confused with other genetic disorders [12]. The human HL gene, a 60 kb gene with a 1.6 kb exon, is present on chromosome 15 [13,14]. The gene

© 2011 Pulchinelli et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.