PubMed Health⌕ Search

Biomedical subjects

D Corella

Publications and source records attributed to D Corella.

35 records · Page 2Linked to original sources

Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population.

Genetic variants at the cholesteryl ester transfer protein (CETP) locus have been associated with CETP activity and mass, as well as plasma high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels. We have examined allele frequencies and lipid associations for the common CETP TaqIB polymorphism in a sample of 514 healthy subjects (231 men, mean age 37.4 years, and 283 women, mean age 35.7 years) residing in Valencia (Spain). The frequency of the less common TaqIB2 allele (0.351; 95% CI: 0.322-0. 380) was significantly lower than those reported for Northern European populations. Consistent with previous studies, we found a significant association of the TaqIB polymorphism with HDL-C levels. Homozygotes for the B1 allele had lower HDL-C levels than subjects carrying the B2 allele (P trend<0.001 and 0.002, for men and women, respectively). No statistically significant genotype effects were observed for any of the other lipid measures. Multivariate models including TaqIB genotype, body mass index, smoking, alcohol, physical activity, marital status and education were fitted to predict HDL-C levels. The TaqIB polymorphism was consistently an independent predictor of HDL-C levels (P<0.001), and explained 5.8% of its variance. To evaluate gene-environmental interactions, first order interaction terms were tested into the multivariate model. No statistically significant interactions between the TaqIB genotypes and smoking, alcohol, physical activity or education were detected. In conclusion, we observed a significant association of the TaqIB polymorphism with HDL-C levels, which remained consistent across different levels of behavioral factors. Moreover, we found that the TaqIB2 allele frequency was lower in our sample than in other European populations, which could be a contributing factor to the unexpectedly high prevalence of coronary heart disease observed in the region of Valencia.

Adolescent↗

Cancer mortality and exposure to chemical carcinogens in the work place: an ecological study in the Valencian Community, Spain (1981-1995).

To evaluate the geographical distribution of the mortality from malignant tumours in relationship with exposure to chemical carcinogens in the work place, and to asses the possible association between these questions and the percentage of population employed in certain high-risk sectors, an ecological study in the Valencian Community (VC), Spain was carried out. Age-adjusted mortality rates for the total number of malignant tumours, lung, bladder, lymphomas and leukaemia during the periods 1981-1985 and 1991-1995 were calculated for the 34 geographical areas. The percentage of population in each area working in sectors in which they may be exposed to chemical carcinogens was obtained. The relationship between mortality on-the-job exposure was studied using linear regression methods. Large differences in cancer mortality were seen. In men, the geographical pattern was very stable and reveals a significant association with the distribution of certain high-risk jobs. Statistically significant positive correlations (p < 0.001) were found between cancer mortality and the percentage of the population working in metal, wood and furniture sectors. In contrast, a negative and statistically significant (p < 0.001) correlation was observed between cancer mortality and the percentage of the population working in agriculture. In conclusion, although the variability in cancer mortality in men was significantly associated with some occupational sectors in the VC, caution is needed when drawing conclusions about causation from ecological studies.

Agriculture↗

Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (P<0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.

Adult↗

Risk of venous thrombosis in carriers of the prothrombin G20210A variant and factor V Leiden and their interaction with oral contraceptives.

BACKGROUND AND OBJECTIVES: The prothrombin G20210A mutation and factor V Leiden have been found to be associated with an increased risk of venous thrombosis, but the reported prevalences of the prothrombin gene variant both in the normal population and in patients with deep venous thrombosis (DVT) vary greatly in the literature. Moreover, the influence of oral contraceptives (OC) on thrombotic events in patients with the prothrombin G20210A variant has not been well established. In this study we evaluate both circumstances. DESIGN AND METHODS: A case-control study was run on 229 patients with DVT and 246 healthy controls. The patients' history of thrombosis and acquired thrombotic risk factors, especially OC, were recorded. Prothrombin G20210A mutation, factor V Leiden, antithrombin, heparin II cofactor, plasminogen and proteins C and S were evaluated. RESULTS: Seven and a half percent of the patients and 2.9% of the controls were carriers of the prothrombin mutation, while 12.2% of the patients and 1.6% of the controls had factor V Leiden. Among the 229 DVT patients there were 130 patients with clinically suspected thrombophilia (first thrombotic event occurring before the age of 45 years or positive family history of thrombosis or recurrent venous thrombosis). Ten percent of these 130 patients were carriers of the prothrombin G20210A mutation and 18.5% had the factor V Leiden mutation. The odds ratios (OR) for DVT risk were: 2.4 (95% CI, 1.0-6.3) for the total DVT patients and 5.2 (95% CI, 1.4-19.5) for the patients with clinically suspected thrombophilia with the prothrombin mutation. The risk of thrombosis was 6.9 (95% CI, 2.3-20.6) for the DVT patients and 14.3 (95% CI, 3.3-64.6) for the patients with clinically suspected thrombophilia with factor V Leiden. Fifty-five percent of the patients with combined congenital defects (prothrombin mutation G20210A plus another congenital defect) had recurrent thrombosis. In women receiving OC the risk of DVT was 3.5 (95% CI, 1.5-8.2) that of the patients not receiving OC. When women with combined defects were also taking OC, the risk of thrombosis increased significantly. INTERPRETATION AND CONCLUSIONS: The prevalence of the prothrombin G20210A mutation in the healthy population in our study is similar to that observed in other southern European countries. The prothrombin G20210A mutation does not by itself seem to be a high thrombotic risk factor. However, when it is present together with other thrombotic risk factors, the predicted risk of thrombotic events increases. The use of OC by women with the prothrombin G20210A variant or FV Leiden, either alone or combined with other thrombotic risk factors, was associated with a significant increase in the risk of venous thrombosis.

Adult↗

[Genetic and molecular study of cystinuria in the Valencian community].

BACKGROUND: The aim of this study has been to know the prevalence of the four most common mutations reported in SLC3A1 gene involved in human cystinuria, and to estimate the association with different phenotypic manifestations of this disease in population of the Valencian Community, Spain. PATIENTS AND METHODS: We have carried out a cross-sectional study with a control group in 16 families with one or more members diagnosed as cystinuric patients. 149 subjects (38 cystinuric patients, 39 relatives and 72 controls) were studied. Genetic analyses were carried out using PCR (polymerase chain reaction), RFLPs (restriction fragment length polymorphisms) and sequencing of PCR products. Parametric and non parametric tests were applied in the statistical analyses. RESULTS: None of the four mutations studied were found in the control group. M467T mutation was the most prevalent in cystinuric patients as well as in relatives, showing and allelic frequency of 0.06 and 0.03 respectively. Regarding to the association analysis between genotype and phenotype, we found that, in cystinuric subjects, urinary excretion of some dibasic amino acid was higher in those who carried M467T mutation (p < 0.05). The formation of cystine crystals was also higher in cystinuric patients who carried this mutation (p < 0.05). CONCLUSIONS: Prevalences of recurrent mutations reported up to now in SLC3A1 gene are very low in cystinuric subjects of the Valencian Community, Spain. Only mutation M467T has been found, without differences between cystinuric and their relatives, although in the first ones was associated with a more accurate phenotype manifestation of the disease.

Adolescent↗

Reference values of urinary excretion of cystine and dibasic aminoacids: classification of patients with cystinuria in the Valencian Community, Spain.

OBJECTIVE: Cystinuria is an autosomal-recessive disorder of the kidneys and small intestine affecting a luminal transport mechanism shared by cystine, ornithine, arginine, and lysine. Three different types of cystinuria can be distinguished according to the excretion of these amino acids in urine samples. We propose cutoff values from our population as references and we present a classification of cystinuric patients using quantitative amino acid chromatography in first morning urine samples. DESIGN AND METHODS: A random sample of forty healthy subjects belonging to general population of the Valencian Community were selected as control subjects. Cystine, lysine, arginine, and ornithine were quantified by reverse-phase HPLC. Seventy-two subjects, diagnosed previously as cystinuric by the cyanide-nitroprusside test were classified. Probands excreting more than 113.12 micromol cystine per mmol of creatinine (i.e., 1,000 micromol cystine per gram of creatinine) were classified as homozygotes. Parents of homozygotes in whom excretion of amino acids were normal were classified as heterozygotes type I. Those probands showing the excretion of at least one amino acid and the sum of urinary cystine plus the basic amino acids higher than the corresponding references ranges in our population were classified as heterozygotes type II or type III (heterozygotes non-type 1). RESULTS: We identified 24 homozygotes, 39 non-type I heterozygotes and 3 type I heterozygotes. The remaining 6 probands could not be classified. Means for cystine, lysine, arginine ornithine and their sum in homozygotes and heterozygotes non-type I were significantly (p < 0.001) in excess of the respective reference ranges. Moreover, means values in homozygotes were statistically different (p < 0.001) from heterozygotes non-type I. CONCLUSION: Urinary excretion of cystine per mmol creatinine allow us to distinguish heterozygotes from homozygotes. However, the best discriminator to distinguish non-type I heterozygotes from normal population might be the excretion of lysine per mmol creatinine. Additional studies including characterization of appropriate haplotypes should be carried out for a more precise identification of types of cystinuria.

Adolescent↗

Association of polymorphisms at the SR-BI gene locus with plasma lipid levels and body mass index in a white population.

The scavenger receptor class B type I (SR-BI) is a lipoprotein receptor that has been shown to be important in high density lipoprotein cholesterol (HDL-C) metabolism in mice. To determine its role in humans, we have characterized the human SR-BI gene and investigated its genetic variation in 489 white men and women. Five variants were demonstrated: 2 in introns (3 and 5) and 3 in exons (1, 8, and 11). Three variants at exons 1 and 8 and intron 5 with allele frequencies >0.1 were used to examine associations with lipid or anthropometric variables. The exon 1 variant was significantly (P<0.05) associated with increased HDL-C and lower low density lipoprotein cholesterol (LDL-C) values in men, but no associations were observed in women. The exon 8 variant was associated in women with lower LDL-C concentrations (3.05+/-0.98 mmol/L and 3.00+/-0.93 mmol/L for heterozygotes and homozygotes, respectively) compared with women homozygous for the common allele (3.39+/-1.09 mmol/L, P=0. 043). No associations for this variant were observed in men. Women carriers of the intron 5 variant showed a higher body mass index (23. 8+/-3.8 kg/m2, P=0.031) than those women homozygous for the common allele (22.4+/-3.4 kg/m2). Similar results were observed after haplotype analysis. Multiple regression analysis using HDL-C, LDL-C, and body mass index as dependent variables and age, sex, and each of the genetic variants as predictors also provided similar results. The associations found with both LDL-C and HDL-C suggest that SR-BI may play a role in the metabolism of both lipoprotein classes in humans.

Adult↗

[Association of blood uric acid with other cardiovascular risk factors in the male working population in Valencia].

BACKGROUND: Serum uric acid has been reported to be a risk factor for cardiovascular disease (CVD). The objective of the present work was to determine the prevalence of hyperuricemia in a large size sample of a healthy male population, as well as the association between uric acid and other cardiovascular risk factors. PATIENTS AND METHODS: A cross-sectional study was conducted in a randomly selected sample of 1,564 healthy men in Valencia (Spain), aged 20-67 years, working in the automobile industry. Serum values of uric acid, cholesterol, and glucose were obtained, as well as blood pressure and body mass index measurements. An assessment was made of socio-economic data, drug therapy, and smoking. RESULTS: The overall prevalence of hyperuricemia was 5.10%; it increased with age. A marked increase (p < 0.01) of hyperuricemic individuals was observed with increased prevalence of other cardiovascular risk factors (from 1.8% with hyperuricemia alone up to 28% among individuals with four simultaneous risk factors). By means of a multivariate logistic regression analysis, the OR of hyperuricemia associated with each factor were calculated: increased serum glucose was the variable with a stronger association (OR: 2.69; 95%CI: 1.21-5.99), obesity ranking next (OR: 2.50; 95%CI: 1.42-4.49). Statistically significant associations were also observed for increased serum cholesterol, increased blood pressure, and smoking. CONCLUSIONS: The prevalence of hyperuricemia varies with the simultaneous presence of other classical cardiovascular risk factors. Even in this healthy mediterranean population, uric acid is significantly associated with several components in the plurimetabolic syndrome.

Adult↗

Effects of polyamine levels on the degradation of short-lived and long-lived proteins in cultured L-132 human lung cells.

Biogenic polyamines have important regulatory functions in various biological processes and it has also been suggested that they could modulate intracellular protein degradation. For an overall assessment of the role of polyamines in this process, we have investigated the effect that the decrease in intracellular polyamine levels caused by inhibitors of polyamine biosynthesis brings about on the degradation of the pools of short- and long-lived proteins in cultured L-132 human lung cells. Treatment of cells with 100 microM (2R,5R)-delta-methyl acetylenic putrescine (MAP), a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, or with 100 microM MAP plus 50 microM N-butyl 1,3-diaminopropane, a specific inhibitor of spermine synthase, caused a similar decrease (65-70% of control) in the total intracellular levels of polyamines, although they affected the concentrations of spermidine and spermine differently. The effect of the two treatments on protein degradation was essentially the same. In polyamine-depleted cells we observed an inhibition of degradation in long-lived proteins of 16% (P<0.05), with a significant increase in the half-life (t12) of this pool from 100.5 to 120.1 h. This was concomitant with an increase of 26% (P<0. 05) in degradation in short-lived proteins, with a significant decrease in the t12 of this pool from 0.85 to 0.67 h. Recovery of polyamine levels by the addition of 50 microM spermidine to polyamine-depleted cells resulted in a restoration of the degradation rates in both pools of proteins. The way(s) by which polyamines could modulate proteolysis are discussed.

Alkynes↗

Mortality as a function of temperature. A study in Valencia, Spain, 1991-1993.

BACKGROUND: Increased mortality is associated with both very low and very high ambient temperatures. This study assesses the relationship between daily numbers of deaths and variations in ambient temperature within the city of Valencia. METHODS: The daily number of deaths from all causes (total deaths and only those occurring in people aged over 70), as well as those deaths from specific causes (e.g. cardiovascular and respiratory diseases, malignant tumours and all causes except external ones) occurring within the city of Valencia were related to the average daily temperature using autoregressive Poisson regression controlling for seasonality, day of the week, holidays, air pollution, influenza incidence, and humidity. Temperature was measured within the regression model as two complementary variables: 'Heat' and 'Cold'; also taken into account were their delayed effects up to 2 weeks after measurement. RESULTS: Graphical analysis revealed a relationship between temperature and mortality according to the time of year. For the cooler months (November-April), the temperature at which mortality was lowest was the 'minimum' (i.e. around 15 degrees C), while for the warmer months (May-October), it occurred at around 24 degrees C. Because of this, a stratified analysis was undertaken with different values for the 'Heat' and 'Cold' variables according to which of the two seasons was involved. During the colder months of the year, higher temperatures tended to exert a rapid influence on mortality and the lower temperatures a more delayed relation. During the hot season it is the heat variable which more clearly manifests an effect, and this is prolonged over the two following weeks. Variations also occur according to age and cause of death. The effect of temperature is greater in persons aged over 70 years of age, and it is also greater in cases of circulatory and respiratory diseases. CONCLUSIONS: A statistically significant association has been found between temperature and mortality. This relationship is not monotonic, but mortality increases in proportion to the variance in ambient temperature from a range of temperatures that varies from winter to summer.

Cardiovascular Diseases↗

Dietary habits and geographic variation in stomach cancer mortality in Spain.

Following examination of the geographical pattern of stomach cancer incidence in Spain, the possible relationship between diet and stomach cancer has been assessed using an ecological model which looks into the relationship between the consumption of different foods and the nutrient intake in each of the 50 Spanish provinces during the period 1964-65, and the mortality rate for stomach cancer in these same 50 provinces during a period 20 years later (1984-86). The geographical pattern of stomach cancer mortality has been arrived at using the standardized mortality ratios (SMRs) calculated for each province. The per capita consumption of foods was obtained from the National Institute for Statistics and the calculation of nutrient intake was based on tables of nutritional composition. The results have been obtained using the statistical techniques of linear and Poisson regression. Stomach cancer mortality in Spain exhibits a stable and well-defined pattern, with less risk being apparent in the Mediterranean coastal provinces. The variability in the geographical distribution of stomach cancer mortality can, in large part (76%), be explained by the variation in the types of foods consumed between provinces, and this figure rises to 82% when one considers other socio-economic variables. A significant inverse association has been found between gastric cancer mortality and consumption of vegetables, fruits and vegetable oil as well as with vegetative growth and population density. From the multiple regression analysis, which considered both nutritional and socio-economic variables, the strongest inverse association with stomach cancer mortality was found in the consumption of green vegetables. The estimated relative risk (RR) of dying, for an increase in consumption of vegetables of 100 g per capita per day is 0.72, (95% CI: 0.53-0.91). These results are consistent with those of similar studies elsewhere.

Feeding Behavior↗

The effectiveness of health systems in influencing avoidable mortality: a study in Valencia, Spain, 1975-90.

OBJECTIVES: To measure variations in the Holland and Charlton classifications of avoidable death causes and to estimate the effect of the Spanish national health system on avoidable mortality. DESIGN: Mortality in the Valencian Community was assessed between 1975 and 1990. The classifications of Holland and Charlton, used to assess avoidable causes of death, were compared. Holland's classification was then used to divide avoidable mortality into two groups--medical care indicators (MCI), which show the effectiveness of health care, and national health policy indicators (NHPI), which show the status of primary prevention. Comparisons were made with rates, group rates, and population rates. Trends and indices were also studied. SETTING: Valencia, Spain, 1975-90. RESULTS: During the study period, avoidable morality (only assessed by MCI) fell 63%, whereas the remainder of the mortality (non-MCI causes, that is all the non-avoidable causes together with the NHPI group) fell by 17%. If it is assumed that the mortality due to non-MCI causes indicates the overall effect of the environmental, social, nutritional, and genetic influences, then the difference between this and the MCI group would take us nearer the actual effect of the intervention of the health system. CONCLUSIONS: It is concluded that in this community, the health system has been responsible for approximately 47% of the total reduction in mortality from avoidable causes in the period studied.

Adolescent↗

Air pollution and mortality in Valencia, Spain: a study using the APHEA methodology.

STUDY OBJECTIVE: To assess the short term relationship between daily air pollution indicators (black smoke and sulphur dioxide (SO2)) and mortality in Valencia. DESIGN: This was an ecological study using time series data with application of Poisson regression. Daily variations in four selected outcome variables (total mortality, mortality in those over 70 years of age, and cardiovascular and respiratory mortality) were considered in relation to daily variations in air pollution levels for the period 1991-93. SETTING: The city of Valencia, Spain. MAIN RESULTS: The mean daily mortality was 17.5, and the average daily levels of air pollutants from the three monitoring stations included in the study were, 67.7 micrograms/m3 for black smoke, and 39.9 micrograms/ m3 for SO2. A significant positive association between black smoke and three of the four outcomes in the study was found. The estimated relative risk (RR) of dying corresponding to a 10 micrograms/m3 increase in mean daily black smoke over the whole period was 1.009 (95% confidence interval (95% CI): 1.003, 1.015). For mortality in the group aged more than 70 years and for cardiovascular mortality, the RRs were 1.008 (95% CI: 1.001, 1.016) and 1.012 (95% CI: 1.003, 1.022) respectively. The association with SO2 was less clear: it was only evident during the warm season. The estimated RRs in this case were 1.007 (95% CI: 0.999, 1.015) for total mortality, 1.009 (95% CI: 1.00, 1.21) for total mortality in those older than 70, and 1.012 (95% CI: 0.995, 1.026) for cardiovascular deaths. No significant association was found between mortality from respiratory diseases and either of the two pollutants. CONCLUSIONS: A positive relationship between air pollution and mortality was found in the short term, as has been shown in an important number of studies carried out elsewhere. Although the current levels of particulate air pollution in Valencia are not very high, they could have an effect on the number of premature deaths. Despite the fact that the association is weak, it is important at the public health level both because of the numbers of population exposed and the possibility of establishing control measures.

Adolescent↗

A structure-effect study of the induction by polyamines of the transport in vitro of the precursor of ornithine transcarbamylase.

Polyamines induce the transport in vitro of the precursor of ornithine transcarbamylase (pOTC) into isolated rat liver mitochondria by facilitating its functional binding to these organelles. Comparative studies of the effect on the in vitro transport of pOTC of polyamine derivatives and related compounds have allowed us to establish that: (i) at least two protonated amino groups per molecule are necessary to induce the pOTC transport; (ii) a distance of three -CH2- groups between the amino groups in diamines is enough to induce this effect, although no differences were observed with diamines having distances of three to eight -CH2- groups. Longer distances resulted in a marked decrease of the effect.

Animals↗

[Mortality from childhood and adolescent leukemia in Spain (1951-1985)].

PURPOSE: To study the mortality due to leukaemia during childhood and youth in Spain in the period 1951-1985. MATERIAL AND METHODS: The mortality for all types of leukaemia in that period was studied in three aspects: (a) By reviewing the rates of specific mortality for ages under 20 years, at quinquennial intervals and per millions of inhabitants of those ages. (b) Studying the mortality per cohorts of births at five-year intervals from 1951-1955 to 1981-1985. (c) Attaining the statistical value, "observed deceased" of leukaemia in people under 15 years of age for the period studied and on each year of that period, and comparing such value with the number of "expected deceased", with regard to the reference year, 1965. RESULTS: A decreasing trend was observed along the whole period. As for ages, there seems to be some tendency to stabilisation of the mortality in the last five-year period, 1981-1985 (there is a decrease only in the 15-18 age-group). These data were confirmed when assessing the mortality per "birth cohorts" or generations, and after plotting the figures of "observed" and "expected" mortality in accordance with the previous evolution. CONCLUSION: It was inferred that regard to the mortality of childhood and youth leukaemia, in Spain the situation has improved markedly, doubtless as a result of better therapeutical approach. This evolution closely resembles the patterns of the most developed countries from a sanitary standpoint.

Adolescent↗

Dietary habits and epidemiology of gastric carcinoma.

Gastric carcinoma has been the primary cause of cancer incidence worldwide until the early eighties. However, its incidence and mortality rates have been declining in most areas of the world over the last decades. This pattern of trends may reflect important changes in lifestyle linked to socioeconomic factors (refrigeration of stored foods, water supply, decline of infections and dietary habits). This article reviews the changing epidemiology of gastric carcinoma including time trends, pathological considerations, and international distribution as well as the main methodological difficulties of the studies about the relationships between dietary habits and gastric carcinoma.

Africa↗