Biomedical subjects

Dolores Corella

Publications and source records attributed to Dolores Corella.

49 records · Page 3Linked to original sources

PubMed2003

[Low prevalence of the Leu7/Pro polymorphism in the signal peptide of preproneuropeptide Y in the Spanish Mediterranean population].

BACKGROUND AND OBJECTIVE: A common Leu7Pro polymorphism in the signal peptide of neuropeptide Y has been associated with increased plasma cholesterol and accelerated atherosclerosis in the Finnish population. SUBJECTS AND METHOD: A cross-sectional design was carried out in 1,000 individuals from the Mediterranean Spanish population to estimate its prevalence. Two independently collected samples consisting of 486 subjects (sample 1) and 514 subjects (sample 2) were studied. The Leu7Pro polymorphism was determined. RESULTS: We found only one individual carrying the Leu7Pro variant (0.1%). The allele frequency of the Pro7 allele was extremely low: 0.005 (95% CI,0.0001-0.0015). CONCLUSIONS: This low prevalence suggests that the Pro7 allele is not one of the genetic determinant factors affecting obesity, plasma lipids or alcoholism in this population.

Adolescent↗

PubMed2003

Obesity modulates the association among APOE genotype, insulin, and glucose in men.

OBJECTIVE: Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels. RESEARCH METHODS AND PROCEDURES: From 1991 to 1995, 3799 subjects underwent a clinical examination and fasting insulin and glucose measurement. APOE genotypes were determined on 3500 participants. Participants taking oral hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were excluded. Finally, 2929 individuals were included in the present analysis. RESULTS: In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in nonobese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, the effect of interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose. DISCUSSION: Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.

Apolipoproteins E↗

PubMed2003

Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey.

We have previously reported an interaction between -514C>T polymorphism at the hepatic lipase (HL) gene and dietary fat on high-density lipoprotein-cholesterol (HDL-C) metabolism in a representative sample of white subjects participating in the Framingham Heart Study. Replication of these findings in other populations will provide proof for the relevance and consistency of this marker as a tool for risk assessment and more personalized cardiovascular disease prevention. Therefore, we examined this gene-nutrient interaction in a representative sample of Singaporeans (1324 Chinese, 471 Malays and 375 Asian Indians) whose dietary fat intake was recorded by a validated questionnaire. When no stratification by fat intake was considered, the T allele was associated with higher plasma HDL-C concentrations (P = 0.001), higher triglyceride (TG) concentrations (P = 0.001) and higher HDL-C/TG ratios (P = 0.041). We found a highly significant interaction (P = 0.001) between polymorphism and fat intake in determining TG concentration and the HDL-C/TG ratio (P = 0.001) in the overall sample even after adjustment for potential confounders. Thus, TT subjects showed higher TG concentrations only when fat intake supplied >30% of total energy. This interaction was also found when fat intake was considered as continuous (P = 0.035). Moreover, in the upper tertile of fat intake, TT subjects had 45% more TG than CC individuals (P < 0.01). For HDL-C concentration, the gene-diet interaction was significant (P = 0.015) only in subjects of Indian origin. In conclusion, our results indicate that there are differences in the association of -514C>T polymorphism with plasma lipids according to dietary intake and ethnic background. Specifically, the TT genotype is associated with a more atherogenic lipid profile when subjects consume diets with a fat content > 30%.

Asian People↗

PubMed2003

Genetic variation at the scavenger receptor class B type I gene locus determines plasma lipoprotein concentrations and particle size and interacts with type 2 diabetes: the framingham study.

The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transport pathway. We have previously reported three common polymorphisms associated with plasma lipids and body mass index. We hypothesized that diabetic status may interact with these polymorphisms in determining plasma lipid concentrations and particle size. We evaluated this hypothesis in 2463 nondiabetic (49% men) and 187 diabetic (64% men) participants in the Framingham Study. SR-BI and APOE genotypes, anthropometric, clinical, biochemical, and lifestyle variables were determined. After multivariate adjustment, we found a consistent association between the exon 8 polymorphism and high-density lipoprotein cholesterol concentration and particle size. Interaction effects were not significant for exon 8 and intron 5 polymorphisms. However, we found statistically significant interactions between SR-BI exon 1 genotypes and type 2 diabetes, indicating that diabetic subjects with the less common allele (allele A) have lower lipid concentrations. For low-density lipoprotein cholesterol, the adjusted means (+/-SE) were 3.31 +/- 0.03 and 3.29 +/- 0.04 mmol/liter for G/G and G/A or A/A in nondiabetics, respectively, compared with 3.19 +/- 0.10 and 2.75 +/- 0.01 mmol/liter for G/G and G/A or A/A in diabetics (P = 0.03 for interaction). Similar results were obtained for HDL(2)-C. In conclusion, SR-BI gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects.

Alleles↗

PubMed2003

Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk.

The role played by a hypercoagulable state, either inherited or acquired, in the pathogenesis of upper-extremity deep vein thrombosis (UEDVT) remains a question of debate. We performed a case-control study including 79 patients with a first objectively confirmed episode of UEDVT, 31 secondary and 48 primary, and 165 healthy controls. Nine patients (11.4%) with UEDVT were carriers of the prothrombin G20210A mutation vs. six (3.7%) in controls; P = 0.025, OR: 3.39 (95% CI 1.16 to 9.88). No statistical difference was observed between cases and controls for the factor V Leiden mutation, AT, protein C or protein S deficiency and anticardiolipin antibodies (ACAs). Thirteen (35.1%) UEDVT patients were oral contraceptive (OC) users vs. 12 (16%) controls; P = 0.020, OR: 2.89 (95% CI 1.16-7.21). When secondary UEDVT patients were compared with controls, no differences were observed in any of the risk factors analysed. On the other hand, when primary UEDVT was considered, six (12.5%) patients were carriers of the prothrombin G20210A mutation vs. six (3.7%) controls; P = 0.031, OR: 3.76 (95% CI 1.15-12.26). Regarding ACAs, a borderline statistical significance was observed when primary UEDVT was compared with controls, P = 0.048; OR: 4.88 (95% CI 1.05-22.61). In primary UEDVT, 52% of the fertile women were OC users vs. 16% of controls; P = 0.001, OR: 5.78 (95% CI 2.13-15.67). When the interaction of both factors, i.e. prothrombin G20210A mutation and OC intake, were considered, the risk increased markedly, indicating a synergistic effect as observed with other thrombotic locations. In patients with primary UEDVT screening for antithrombin, protein C and protein S deficiency and APC resistance would not be justified, although it might be reasonable to determine the carrier status of the prothrombin G20210A mutation only in OC users.

Adolescent↗

PubMed2002

Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism: evidence of a strong dose effect in this gene-nutrient interaction in the Framingham Study.

BACKGROUND: Gene-nutrient interactions affecting high-density lipoprotein cholesterol (HDL-C) concentrations may contribute to the interindividual variability of the cardiovascular disease risk associated with dietary fat intake. Hepatic lipase (HL) is a key determinant of HDL metabolism. Four polymorphisms in linkage disequilibrium have been identified in the HL gene (LIPC), defining what is known as the -514T allele. This allele has been associated with decreased HL activity and increased HDL-C concentrations. However, the effect is variable among populations. METHODS AND RESULTS: We have examined interaction effects between the -514(C/T) LIPC polymorphism, dietary fat, and HDL-related measures in 1020 men and 1110 women participating in the Framingham Study. We found a consistent and highly significant gene-nutrient interaction showing a strong dose-response effect. Thus, the T allele was associated with significantly greater HDL-C concentrations only in subjects consuming <30% of energy from fat (P<0.001). When total fat intake was > or =30% of energy, mean HDL-C concentrations were lowest among those with the TT genotype, and no differences were observed between CC and CT individuals. We found similar gene-nutrient interactions when the outcome variables were HDL2-C (P<0.001), large HDL subfraction (P<0.001), or HDL size (P=0.001). These interactions were seen for saturated and monounsaturated fat intakes (highly correlated with animal fat in this population), but not for polyunsaturated fat. CONCLUSIONS: Dietary fat intake modifies the effect of the -514(C/T) polymorphism on HDL-C concentrations and subclasses. Specifically, in the Framingham Study, TT subjects may have an impaired adaptation to higher animal fat diets that could result in higher cardiovascular risk.

Adult↗

PubMed2002

[Effects of the apolipoprotein E polymorphism on plasma lipid levels and cardiovascular disease risk in a Mediterranean population].

BACKGROUND: Association of apolipoprotein E (apo E) polymorphism with atherosclerosis varies among populations. Our aim was to estimate the association of common apo E variants (epsilon2, epsilon3 and epsilon4 alleles) with plasma lipid concentrations and cardiovascular disease (CAD) risk in a Spanish Mediterranean population. PATIENTS AND METHOD: This was a cross-sectional study in 486 subjects (144 men and 342 women)from a general Mediterranean population (7-85 years). Apo E genotypes,anthropometric, biochemical and life-style variables were determined. RESULTS: Frequency of epsilon2 and epsilon4 alleles was low (0.052; 95% CI, 0.038-0.066, and 0.063; 95% CI,0.048-0.078, respectively). Apo E polymorphism was associated (p = 0.016) with LDL-C concentrations (119.9; 138.1 and 146.6 mg/dl in carriers of the epsilon2, epsilon3/epsilon3,and epsilon4 alleles, respectively). These differences remained significant (p = 0.017) after adjustment for gender, age and life-style factors. Subjects carrying the epsilon2 allele had higher triglyceride concentrations than non-carriers (p = 0.019). Prevalence of CAD was 14.0% in epsilon4 carriers, 6.9% in epsilon2 carriers and 3.4% in epsilon3/epsilon3 homozygotes. The higher risk of CAD associated with the epsilon4 allele remained significant (OR = 5.88; 95% CI, 1.64-21.02) after adjustment for gender, age and life-style factors. CONCLUSIONS: In the Spanish Mediterranean population, epsilon4 allele was associated with higher LDL-C concentrations and with a higher risk of CAD.

Adolescent↗

PubMed2002

Hyperlipidaemia and venous thromboembolism in patients lacking thrombophilic risk factors.

To ascertain the potential contribution of serum lipids to the development of deep vein thrombosis (DVT), a case-control study was conducted in 143 DVT patients lacking thrombophilic risk factors and in 194 age- and sex-matched controls. DVT patients showed significantly higher body mass indices (BMI), and triglyceride levels than did controls (P < 0.001 and P = 0.045 respectively). Using multivariate analysis, BMI was the only variable which remained statistically different, thus the risk of DVT was associated with obesity (odds ratio = 2.49). These results were confirmed when additional control for fibrinogen and plasminogen activator inhibitor type 1 (PAI-1) was carried out in a subgroup of cases and controls. When idiopathic (n = 39) and secondary (n = 104) patients with DVT were compared, the former showed a higher mean age, a higher proportion of men, and higher cholesterol levels. Age, sex and total cholesterol were statistically different by multivariate analysis. After age was dichotomized as >or= 50 years and cholesterol >or= 5.69 mmol/l, all three variables constituted independent risk factors for idiopathic DVT, with odds ratios of 2.73 for ages >or= 50 years; 3.72 for men and 2.67 for cholesterolaemia >or= 5.69 mmol/l. Obesity thus constitutes an independent risk factor for DVT, possibly in part mediated through triglyceride, fibrinogen and PAI-1 effects on haemostasis. In addition, cholesterolaemia levels of >or= 5.69 mmol/l constitute an independent risk factor for idiopathic DVT.

Adult↗

PubMed2002

Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study.

BACKGROUND: A common G-to-A substitution in the promoter area (-75 base pairs) of the apolipoprotein A-I gene (APOA1) has been described. The A allele was shown to be associated with higher HDL-cholesterol concentrations in some studies but not in others. OBJECTIVE: We examined whether dietary fat modulates the association between this polymorphism and HDL-cholesterol concentrations. DESIGN: We studied a population-based sample of 755 men and 822 women from the Framingham Offspring Study. RESULTS: The frequency of the A allele was 0.165. No significant differences were observed between G/G subjects and carriers of the A allele for any lipid variables. In multivariate linear regression models, HDL-cholesterol concentrations in women were associated with a significant interaction between polyunsaturated fatty acid (PUFA) intake as a continuous variable and APOA1 genotype (P = 0.005). By using 3 categories of PUFA intake, we found a significantly different effect of APOA1 genotype across PUFA categories in women. When PUFA intake was <4% of energy, G/G subjects had approximately 14% higher HDL-cholesterol concentrations than did carriers of the A allele (P < 0.05). Conversely, when PUFA intake was >8%, HDL-cholesterol concentrations in carriers of the A allele were 13% higher than those of G/G subjects (P < 0.05). No significant allelic difference was observed for subjects in the range of PUFA intake of 4-8% of energy. These interactions were not significant in men. CONCLUSIONS: We found a significant gene-diet interaction associated with the APOA1 G-A polymorphism. In women carriers of the A allele, higher PUFA intakes were associated with higher HDL-cholesterol concentrations, whereas the opposite effect was observed in G/G women.

Adult↗

PubMed2002

Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a Mediterranean population: interaction with tobacco smoking and the APOE locus.

We conducted a cross-sectional study in a Spanish population (n = 1,029) to investigate associations between the LPL and APOC3 gene loci (LPL-HindIII, LPL-S447X, and APOC3-SstI) and plasma lipid levels and their interaction with APOE polymorphisms and smoking. Carriers of the H(-) or the X447 allele had higher levels of HDL cholesterol (HDL-C), and lower levels of TG, after adjustment for age, body mass index, alcohol, smoking, exercise, and education (P < 0.01). The APOC3 polymorphism presented additive effects to the LPL variants on TG and HDL-C levels in men, and on TG in women. The most and the least favorable haplotype combinations were H(-)/X447/S1 and H(+)/S447/S2, respectively. These combinations accounted for 7% and 5% of the variation in HDL-C and TG in men, and 3% and 4% in women. There was a significant interaction between APOE and LPL variants and HDL-C levels in both genders (P < 0.05). The increases in HDL-C observed for the rare alleles were higher in epsilon4 than in epsilon3 subjects, and absent in epsilon2 individuals. This effect was modulated by smoking (interaction HindIII-APOE-smoking, P = 0.019), indicating that smoking abolished the increase in HDL-C levels observed in epsilon4/H(-) subjects. Understanding this gene-gene-environmental interaction may facilitate preventive interventions to reduce coronary artery disease risk.

Adult↗

PubMed2002

Biological risk factors for deep vein trombosis.

Hypercoagulable states due either to inherited or acquired thrombotic risk factors are only present in approximately half of cases of DVT, but the causes in the other half, remain unknown. The importance of biological risk factors such as hyperlipidemia, hypofibrinolysis and hemorheological alterations in the pathogenesis of DVT has not been well established. In order to ascertain whether the above mentioned biological factors are associated with DVT and could constitute independent risk factors, we carried out a case-control study in 109 first DVT patients in whom inherited or acquired thrombophilic risk factors had been ruled out and 121 healthy controls age (42+/-15 years) and sex matched. From all the biological variables analyzed (cholesterol, triglycerides, glucose, fibrinogen, erythrocyte aggregation, hematocrit, plasma viscosity and PAI-1) only fibrinogen concentration reached a statistically significant difference on the comparison of means (290+/-73 mg/dl in cases vs 268+/-58 mg/dl in controls, p<0.05). After this continuous variables were dichotomized according to our reference values, the percentage of cases with cholesterolemia >220 mg/dl, hematocrit >45% and fibrinogen >300 mg/dl was higher in cases than in controls: 38% vs 22%; p<0.01; 43% vs 27%; p<0.05; 36% vs 23%; p<0.05, respectively. The percentage of cases with PAI-1 values >30 ng/ml, 37% vs 25% was borderline significant; p=0.055. Multivariate logistic regression analysis showed that cholesterolemia >220 mg/dl and fibrinogen >300 mg/dl constitute independent predictors of venous thrombotic risk. The adjusted OR's were 2.03 (95% CI; 1.12-3.70) for cholesterolemia and 1.94 (95% CI; 1.07-3.55) for fibrinogen. When these two variables combined DVT risk rose about fourfold (3.96; p<0.05). Our results suggest that hypercholesterolemia and hyperfibrinogenemia should be added to the list of known DVT risk factors and we recommend adopting measures to decrease these variables in the population with a high risk of DVT.

Biomarkers↗

PubMed2002

Erythrocyte deformability in survivors of acute myocardial infarction measured by two different methodologies.

In order to ascertain whether erythrocyte deformability (ED) is involved in chronic coronary syndromes, this rheological property was determined in 92 survivors of acute myocardial infarction (AMI) who had had the acute event 3 years ago and in 150 volunteers. From the 92 AMI survivors in 50 (43 males, 7 females aged 61+/-9 years) ED was determined with filtrometric techniques (Hanss Hemorheometre) and in 42 (32 males, 10 females aged 63+/-11 years) with laser diffractometric ones (Rheodyn SSD). The control group consisted of 66 and 84 volunteers whose ED was measured with the above mentioned devices respectively. Patients and controls were matched for age, sex, total cholesterol and triglyceride levels. With the Hanss Hemorheometre, the Rigidity Index (RI) was higher in patients than in controls (9.4+/-1.2 vs 8.7+/-1.5; p=0.01) although after adjusting for confounding variables (MCV and leukocyte count) in a logistic regression analysis the RI was no longer statistically significant. With the Rheodyn SSD the Erythrocyte Elongation Index (EEI) determined at 12, 30 and 60 Pa, did not show statistically significant differences between cases and controls at any of the shear stresses tested. Our results suggest that AMI survivors who had had the ischemic event 3 years ago do not show decrease RBC deformability with either of the two methodologies used. Red blood cell deformability does not appear to contribute to impaired microcirculatory blood flow in chronic coronary syndromes.

Aged↗

PubMedDate not supplied

Influence of social factors on avoidable mortality: a hospital-based case-control study.

OBJECTIVE: The effect of socioeconomic factors on avoidable mortality at an individual level is not well known, since most studies showing this association are based on aggregate data. The purpose of this study was to determine socioeconomic differences between those patients who die of avoidable causes and those who do not die. METHODS: A matched case-control study was carried out regarding in-hospital avoidable mortality (Holland's medical care indicators) that occurred in a university hospital serving a Spanish-Mediterranean population during a 30-month period. RESULTS: We studied 82 cases of death from avoidable causes and 300 controls matched on medical care indicators and age. The variables that showed a statistically significant association with in-hospital avoidable mortality were number of diagnoses (the greater the number, the higher the risk), length of stay (patients staying seven or more days presented a lower risk), and education. Those patients with low and middle educational levels showed a greater risk of avoidable mortality (adjusted odds ratio=3.57 and 2.82, respectively) than those patients with higher levels of education. CONCLUSIONS: Consistent with the findings of studies based on aggregate data, our case-control analyses indicated that among several socioeconomic variables studied, educational level was significantly associated with the risk of in-hospital avoidable mortality, regardless of age and medical care indicators. Patients with low levels of education (<6 years of schooling) were at highest risk for in-hospital avoidable mortality, followed by those with middle levels of education (7-10 years of schooling).

Adolescent↗