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.
Pregnancy-associated melanoma is defined as melanoma diagnosed during pregnancy or within 1 year of delivery. The association of pregnancy with melanoma is well known, but its underlying molecular mechanisms of association are poorly understood. The aim was to assess the expression of apoptosis-related genes in melanoma tumors during pregnancy in an attempt to elucidate the molecular mechanisms underlying apoptosis-driven activation of melanoma cells in this period. Mice were allocated across two experimental groups (nonpregnant and pregnant) and implanted with the melanoma cell line BF16-F10. Tumor tissue was collected for RNA extraction and purification, and gene expression was quantified using the mouse apoptosis RT2ProfilerTM PCR array. Different intracellular apoptotic pathways were activated (positively or negatively) by pregnancy in tumor cells: intrinsic (21.5%), extrinsic (32%), caspase (14%), apoptosis (21.5%), and caspase-activated DNase (11%). The proportion of upregulated genes for each of these pathways was 100, 30, 50, 17, and 0%, respectively. MetaCore software was then used to analyze gene ontology processes and pathways by building networks. Among the gene ontology processes, the majority of differentiated genes were related to the apoptotic process. The main pathway activated by pregnancy was the intrinsic one (genes Api-5, Bcl2-L1, Birc-2, Birc-3, Bok, and Trp53bp2). Pregnancy activates the intrinsic apoptosis pathway to stimulate caspases 7 and 9, but the final balance is inhibition of apoptosis mechanisms. In mice, pregnancy cannot promote or worsen melanoma.
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