Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on the lipoprotein metabolism and insulin resistance in essential hypertensive patients. Interaction between gender and genetic polymorphism

BACKGROUND AND AIM: With respect to the general population, hypertensive patients show an increase in plasma total cholesterol and triglycerides, a decrease in HDL-cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C-III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich lipoproteins. The S2 allele has been associated with elevated plasma triglycerides concentration, blood pressure and increased risk of myocardial infarction, all of which are characteristic of an insulin resistant state. The aim of this study was to investigate the SstI polymorphism of the apo C-III gene locus on the lipoprotein metabolism, apolipoproteins and basal glucose and insulin levels in essential hypertensive patients. We also examined the influence of the S1S2 allele on blood pressure and the interaction of the mutation at the apo C-III gene and the gender. METHODS AND RESULTS: We studied 104 essential hypertensive patients (59 males and 45 females) determining the carriers of the S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain reaction, lipoprotein metabolism by standard laboratory methods and ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal glucose and insulin levels by enzymatic method and radioimmunoassay, respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2 genotype) was 0.17. Patients with the rare S2 allele compared with those with S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/- 34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group. Subgroup analysis revealed that the association between these polymorphism and lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels occurred predominantly in females. A study on the effect of the interaction between this mutation with gender revealed an additive effect on changes in total triglycerides levels. However age, blood pressure and body mass index were similar in both groups of patients (S1S1 and S1S2 genotypes). CONCLUSIONS: These results provide evidence of interaction between gender and the Sst1 polymorphism of the apo C-III on lipoprotein metabolism and insulin resistance in essential hypertensive patients. However, the studied mutation does not contribute to blood pressure levels in essential hypertensive patients (crossover study).     

Clinical characteristics and head-up tilt test results with three protocols in 1661 patients with syncope

Because of the absence of a uniform protocol for the head-up tilt table test (HUT), we compared 1,661 consecutive patients with syncope referred for HUT. The influence of age and gender on the results (positive response rate and patterns) obtained with three different protocols, Westminster, isoprenaline and nitroglycerin (groups A, B and C) was analyzed. The proportion of women was larger in the youngest age group. A positive response to HUT was observed in 592 patients. The positive response rate to the HUT was higher in groups B and C than in group A, and the rate diminished with age in groups A and C, because of the decrease in mixed-positive responses, but not in group B. The rate of positive responses was similar in groups A and C, but different in group B; no influence of gender on these results was observed. The results with the Westminster and nitroglycerin protocols were similar, but the rate of positive responses was higher in the latter.     

Thermal conditions predict intraspecific variation in senescence rate in frogs and toads

Variation in temperature is known to influence mortality patterns in ectotherms. Even though a few experimental studies on model organisms have reported a positive relationship between temperature and actuarial senescence (i.e., the increase in mortality risk with age), how variation in climate influences the senescence rate across the range of a species is still poorly understood in free-ranging animals. We filled this knowledge gap by investigating the relationships linking senescence rate, adult lifespan, and climatic conditions using long-term capture–recapture data from multiple amphibian populations. We considered two pairs of related anuran species from the Ranidae (Rana luteiventris and Rana temporaria) and Bufonidae (Anaxyrus boreas and Bufo bufo) families, which diverged more than 100 Mya and are broadly distributed in North America and Europe. Senescence rates were positively associated with mean annual temperature in all species. In addition, lifespan was negatively correlated with mean annual temperature in all species except A. boreas. In both R. luteiventris and A. boreas, mean annual precipitation and human environmental footprint both had negligible effects on senescence rates or lifespans. Overall, our findings demonstrate the critical influence of thermal conditions on mortality patterns across anuran species from temperate regions. In the current context of further global temperature increases predicted by Intergovernmental Panel on Climate Change scenarios, a widespread acceleration of aging in amphibians is expected to occur in the decades to come, which might threaten even more seriously the viability of populations and exacerbate global decline.

Studies of age-specific changes in mortality have emphasized that actuarial senescence (i.e., the increase in mortality with age; called “senescence” hereafter) patterns are extremely diverse in the wild (1–3). To date, most studies have been conducted in birds and mammals and have demonstrated that the age at the onset of senescence (4, 5), the rate of senescence (1, 6), and the overall shape of mortality patterns (7, 8) all vary across species. Variation in senescence patterns across species is broadly explained by phylogeny (6), body size (1), and the pace of life (4). Although the genetic and physiological mechanisms modulating among-species variation in senescence are still poorly understood (9), empirical evidence accumulated so far shows that senescence is a ubiquitous phenomenon whose form and intensity vary considerably across the tree of life.In contrast, much less research has focused on variation in senescence patterns across populations within a given species (3). This requires intensive long-term monitoring of multiple populations across a species’ range, which is uncommon. Studies comparing captive and wild populations have shown that controlled environments in zoos slow down the senescence process in mammals (10), with deceleration more pronounced in short-lived than in long-lived species (11). Variation in age-dependent mortality patterns between populations of a given species has also been reported in the wild, suggesting that local environmental conditions (e.g., anthropogenic disturbance, habitat quality) may affect senescence patterns (12–14). However, the influence of environmental variation on the intensity of senescence is still poorly understood in most animal clades (3).Climatic conditions might be a key factor driving intraspecific variation in senescence (15, 16), especially in ectotherms, because their metabolism, activity patterns, and lifespan all strongly depend on temperature (17, 18). Studies of both natural and experimental populations of invertebrates and ectothermic vertebrates have so far revealed that lifespan decreases with increasing ambient temperature (15, 16). In short-lived model organisms, the decrease in lifespan at high temperature is associated with accelerated senescence under laboratory conditions [Caenorhabditis elegans (19), Drosophila melanogaster (20), and Nothobranchius furzeri (21)]. However, lifespan is a trait only partially correlated to senescence rate [e.g., R² < 0.50 in mammals (22)], which does not reliably reflect age-specific mortality patterns (9). To date, a link between senescence and climate has not been demonstrated in the wild, which limits our ability to assess the universality of this relationship and prevents reliable predictions about the influence of climate change on senescence.Amphibians are excellent biological models to investigate the influence of climatic conditions on senescence patterns in nature. Previous studies have shown that as temperatures decrease along altitudinal and latitudinal gradients, the pace of life of amphibians slows down, involving delayed sexual maturity, less frequent egg deposition by females, and increased lifespan (23, 24); this slow pace of life is expected given the ecological effects of altitude in most taxa (25). At higher altitudes and latitudes, individuals maximize survival in cold conditions by reducing their activity period and placing themselves into an hypometabolic state that minimizes their energy expenditure (26, 27). At lower altitudes and latitudes, the activity period is longer (23); overall, metabolic activity increases, and warm conditions both diminish mitochondrial efficiency and accelerate the accumulation of oxidative damages (28), possibly leading to an earlier or faster senescence. This effect may be amplified by evaporative water loss that reduces the capacity of cutaneous respiration (29) and body temperature regulation (30) when individuals experience hot temperatures and low precipitation. These phenomena could have synergistic effects on age-dependent mortality, resulting in an acceleration of senescence with increasing temperature and decreasing precipitation.To assess the relationship between age-specific mortality patterns and climatic conditions, we measured the influence of temperature and precipitation on among-population variation in senescence rate and adult lifespan in two pairs of frog and toad species from the Ranidae and Bufonidae families, which diverged more than 100 Mya (31). We focused on four species widely distributed in North America (Columbia spotted frog, Rana luteiventris, and Boreal toad, Anaxyrus boreas; Fig. 1) and Europe (common frog, Rana temporaria, and common toad, Bufo; Fig. 1). To perform these analyses, we took advantage of long-term capture–recapture (CR) data collected in 16 populations of R. luteiventris and A. boreas (eight per species) distributed along a broad climatic gradient in the western United States (Fig. 1 and SI Appendix, Table S1) and in four populations of R. temporaria and B. bufo (two per species) experiencing contrasted temperature conditions in Europe (Fig. 1 and SI Appendix, Table S1). More specifically, we tested whether warmer mean annual temperature was associated with higher senescence rate and shorter adult lifespan and, similarly, if higher mean annual precipitation was correlated with lower senescence rate and longer adult lifespan. As human activities may also influence local mortality patterns in amphibians (13, 32), we took into account the intensity of human footprint by including a quantitative, empirically based measure of ecological integrity in our models (33) (more details about this metric are given in SI Appendix, Supplementary analysis 1). Furthermore, as sexes may differ in terms of mortality patterns (6, 34) and physiological response to thermal stress, we tested whether the association among senescence, lifespan, and climatic conditions differed between males and females.Open in a separate windowFig. 1.Study system used to test the links among actuarial senescence rate, lifespan, and climatic conditions in four amphibian species from North America (Columbia spotted frog, R. luteiventris, and Boreal toad, A. boreas) and Europe (common frog, R. temporaria, and common toad, B. bufo). (A) Calibrated phylogenetic tree (retrieved from ref. 63, http://www.timetree.org/) presenting the phylogenetic relationships and divergence time among the four species; the African clawed frog (Xenopus laevis) was used as an outgroup. (B and C) Maps with background showing mean annual temperature (A) and mean annual precipitation (B) in the western United States (extracted from https://adaptwest.databasin.org). (D and E) Maps with background showing mean annual temperature (D) and mean annual precipitation (E) in Europe (extracted from https://www.worldclim.org/).     

Quality of life in patients with oral and oropharyngeal cancer

Quality of life (QoL) is an important aspect in the clinical assessment and management of patients with cancer. The aim of the present study was to evaluate QoL at the time of diagnosis in patients with oral and oropharyngeal cancer and to establish the influence of variables such as gender, age, tumor location and tumor staging. The authors studied 149 patients with oral and oropharyngeal cancer for 2 years. QoL was measured using the EORTC QLQ-C30 and its specific modules for head and neck cancer QLQ-H&N 35. Variable deterioration of QoL was observed before therapy. The emotional domain showed the greatest alterations, while pain was the most remarkable symptom variable. QoL seems to be associated with gender (female patients obtained worse scores in most of the functional scales), age (patients < 65 years scored better), tumor location (orpharyngeal tumors showed worse prognosis) and tumor staging (early stages obtained better scores than advances ones). Many patients with oral and oropharyngeal cancer show poor QoL before initiating treatment. The present study of a homogeneous group of patients is the first carried out in Spain following the EORTC QLQ-C30 questionnaire and its results may serve for future reference. These results are similar to those obtained in populations from the north and centre of Europe.