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

Abstract

BackgroundHepatic 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).ResultsStatistically 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.ConclusionsThe variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.

Estrogen lowers triglyceride via regulating hepatic APOA5 expression

“…Whitcroft et al [4] reported that transdermal estradiol treatment for post-menopausal women could lower serum TG levels by about 16.4% ( P  < 0.01). Pulchinelli et al [5] found that estrogen replacement therapy statistically reduced TG levels of hysterectomized women. A meta-analyzed further confirmed a modest effect of transdermal estradiol treatment on decrease of serum TG levels [6].…”

Lack of Association between Polymorphisms of Hepatic Lipase with Lipid Profile in Young Jordanian Adults

“…14,15,17,20,21,[37][38][39] However, the G-250 and C-514 alleles are relatively less frequent in Japanese, Iranians, Chinese, Koreans, Americans, and Brazilians. 7,8,12,13,18,19,[22][23][24][25]40,41 In this study, only two polymorphisms in LIPC gene were examined. However, other LIPC gene variants, such as C-480T, are associated with lipid profile and CVDs.…”

“…[7][8][9][10][11][12][13] Both C-514T and G-250A SNPs are associated with cardiovascular diseases (CVDs). [14][15][16][17][18] The distribution and clinical significance of LIPC C-514T and G-250A polymorphisms have been extensively investigated among the Europeans, Asians, and Americans, 12,13,15,17,[19][20][21][22][23][24][25] while they are still widely unknown among Arabs. Therefore, in this study, LIPC C-514T and G-250A polymorphisms and association with plasma lipid profile in young Jordanians were investigated.…”

Ovarian Hormonal Change-Related Energy Metabolism and Obesity in Menopausal Women

“…The underlying mechanisms that estrogen and lipid interact at a molecular level to contribute to the risk of CVD are not clear. It has been reported that estrogenrelated receptor γ (ERRγ) regulates hepatic TG metabolism through the action phospholipase A2G12B [44], and polymorphic hepatic lipase is associated with estrogen modulate lipolysis of TG [45]. Della Torre et al showed that liver ERα activity was essential for balanced lipid and TC metabolism, lack of ERα might lead to hepatic fat accumulation and nonalcoholic fatty liver disease [46].…”

“…Numerous studies have attempted to understand the metabolic consequences of MHT use and define the effects of different MHT regimens. Major studies have consistently found MHT decrease LDL-C, TC and lipoprotein (a) levels; however, findings regarding TG and HDL-C levels have been inconsistent [45,[54][55][56][57]. Godsland reviewed the effect of different MHT regimens, estrogen alone, estrogen plus progestogen, raloxifene, or tibolone on plasma lipid and lipoprotein levels and found estrogen alone raise HDL-C and lower LDL-C and TC.…”