The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

<p>Abstract</p> <p>Background</p> <p>Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (<it>FADS</it>) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date.</p> <p>Results</p> <p>In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10^-48) and lower DGLA levels (p = 9.80 × 10^-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (<it>FADS</it>) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10^-16in African Americans, 2.68 × 10^-23in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with <it>enhanced </it>conversion of DGLA to AA, on enzymatic efficiency was similar in both groups.</p> <p>Conclusions</p> <p>We conclude that the impact of <it>FADS </it>genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.</p

Holocene sea level fluctuations and coastal evolution in the central Algarve (southern Portugal)

In Armação de Pêra Bay, southern Portugal, environmental changes during the Holocene can be interpreted based on the morphological and sedimentological similarities between older geomorphic features (cemented beach and dune rocks) and present coastal features. Using knowledge of the present beach and dune processes, we propose a two-step model for the evolution of Armação de Pêra Bay. First, during the rapid sea level rise between about 8800 and 6600 yr cal BP, the bay changed from a positive to a negative budget littoral cell and transgressive dunes formed, favoured by drought conditions. At about 5000 yr cal BP, during a sea level maximum, beach width was less than the critical fetch and dunes stabilized and underwent cementation during the wetter Atlantic climatic event. The second phase of dune accumulation started at about 3200 yr cal BP, due to a regression of sea level during which the bay changed back to a positive budget littoral cell in which beach width was greater than the critical fetch. Currently, the beach width is less than the critical fetch, dunes are inactive, and the sedimentary budget is negative due to sediment storage in local river systems.Fundação para a Ciência e a Tecnologia. FEDER, and OE (Project POCTI/CTA/34162/2000

Effects of aldosterone on transient outward K+ current density in rat ventricular myocytes

Aldosterone, a major ionic homeostasis regulator, might also regulate cardiac ion currents. Using the whole-cell patch-clamp technique, we investigated whether aldosterone affects the 4-aminopyridine-sensitive transient outward K+ current (Ito1).Exposure to 100 nm aldosterone for 48 h at 37 °C produced a 1.6-fold decrease in the Ito1 density compared to control myocytes incubated without aldosterone. Neither the time- nor voltage-dependent properties of the current were significantly altered after aldosterone treatment. RU28318 (1 μm), a specific mineralocorticoid receptor antagonist, prevented the aldosterone-induced decrease in Ito1 density.When myocytes were incubated for 24 h with aldosterone, concentrations up to 1 μm did not change Ito1 density, whereas L-type Ca2+ current (ICa,L) density increased. After 48 h, aldosterone caused a further increase in ICa,L. The delay in the Ito1 response to aldosterone might indicate that it occurs secondary to an increase in ICa,L.After 24 h of aldosterone pretreatment, further co-incubation for 24 h either with an ICa,L antagonist (100 nm nifedipine) or with a permeant Ca2+ chelator (10 μm BAPTA-AM) prevented a decrease in Ito1 density.After 48 h of aldosterone treatment, we observed a 2.5-fold increase in the occurrence of spontaneous Ca2+ sparks, which was blunted by co-treatment with nifedipine.We conclude that aldosterone decreases Ito1 density. We suggest that this decrease is secondary to the modulation of intracellular Ca2+ signalling, which probably arises from the aldosterone-induced increase in ICa,L. These results provide new insights into how cardiac ionic currents are modulated by hormones