ABSTRACT
OBJECTIVE: To determine the prevalence of three single nucleotide polymorphisms (SNPs) in postmenopausal women with and without the metabolic syndrome (METS) and to explore levels of circulating biomarkers of inflammation, vascular and metabolic dysfunction according to SNP genotypes. METHODS: DNA was extracted from the whole blood of 192 natural postmenopausal women (40 to 65 years) screened for the METS and tested for three gene SNPs related to obesity: the fat mass obesity (FTO: rs9939609) and the methylenetetrahydrofolate reductase (MTHFR: C677T and A1298C). Blood levels of angiopoietin, IL-8, sFASL, IL-6, TNF-α, sCD40L, PAI-1, u-PA, leptin, adiponectin, resistin, ghrelin, visfatin, adipsin and insulin were measured in a subgroup, with and without the METS, using multiplex technology (n = 100) and compared according to SNP genotypes. RESULTS: Genotype frequency of the three studied SNPs did not differ in relation to the presence of the METS. However, genotypes CT+TT (C677T) and AT (rs9939609) were more prevalent in women with high triglyceride levels. Pooled sub-analysis (n = 100) found that median sCD40L and visfatin levels were higher in women with genotypes AT+TT (rs9939609) as compared to AA (1178 vs. 937.0 pg/mL and 0.93 vs. 0.43 ng/mL, respectively, p < 0.05). CONCLUSION: Two SNP genotypes related to obesity were more prevalent in women with abnormal triglyceride levels and two vascular and inflammatory serum markers were higher in relation to the rs9939609 SNP.
Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Biomarkers/blood , Inflammation/genetics , Metabolic Syndrome/physiopathology , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Single Nucleotide/genetics , Vascular Diseases/genetics , Adult , Aged , Case-Control Studies , Female , Humans , Inflammation/blood , Metabolic Syndrome/complications , Middle Aged , Obesity/complications , Polymerase Chain Reaction , Postmenopause , Vascular Diseases/bloodABSTRACT
Cell morphology and its interaction with the extracellular environment are integrated processes involving a number of intracellular controllers orchestrating cytoskeletal proteins and their interaction with the cell membrane and anchorage proteins. Sex steroids are effective regulators of cell morphology and tissue organisation, and recent evidence indicates that this is obtained through the regulation of the actin cytoskeleton. Intriguingly, many of these regulatory actions related to cell morphology are achieved through the rapid, nonclassical signalling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton has special relevance for the characterisation of the effects of sex steroids under physiological conditions, such as for the development of neurone/neurone interconnections and dendritic spine density. This is considered to be critical for gender-specific differences in brain function and dysfunction. Recent advancements in the characterisation of the molecular basis of the extranuclear signalling of sex steroids help to clarify the role of oestrogen and progesterone in the brain, and may turn out to be of relevance for clinical purposes. This review highlights the regulatory effects of oestrogens and progesterone on actin cytoskeleton and neurone morphology, as well as recent progresses in the characterisation of these mechanisms, providing insights and working hypotheses on possible clinical applications for the modulation of these pathways in the central nervous system.