Search PubMed⌕ Search

Biomedical subjects

Dolores Corella

Publications and source records attributed to Dolores Corella.

At least 37 records · Page 2Linked to original sources

SINGLE NUCLEOTIDE POLYMORPHISMS THAT INFLUENCE LIPID METABOLISM: Interaction with Dietary Factors.

Cardiovascular disease (CVD) risk is the result of complex interactions between genetic and environmental factors. During the past few decades, much attention has focused on plasma lipoproteins as CVD risk factors. The current evidence supports the concept that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been highly promising. Several loci (i.e., APOA1, APOA4, APOE, and LIPC) are providing proof-of-concept for the potential application of genetics in the context of personalized nutritional recommendations for CVD prevention. However, the incorporation of these findings to the clinical environment is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (i.e., one single dietary component, single nucleotide polymorphism, and risk factor) to more realistic situations involving interactions between multiple genes, dietary components, and risk factors. In summary, there is need for both large population studies and well-standardized intervention studies.

Biological Transport↗

Integration of environment and disease into 'omics' analysis.

Over the last decade, 'omics' technologies have been heralded as 'dream toolboxes' that will make revolutionary changes in disease prevention and treatment possible. However, these expectations have yet to be fulfilled. These promises were made and prospects predicted without full appreciation of the intrinsic complexity of common diseases and the significant contribution of environmental factors to disease risk and causation, which have hardly been considered in the omic approaches. The concept of gene-environment interaction, as well as the limitations, difficulties and urgent need to integrate environment into omics analysis are reviewed and discussed.

Delivery of Health Care↗

Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study.

Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; -1131T>C, -3A>G, 56C>G IVS3+ 476G>A, and 1259T>C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C>G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population. SNP analyses revealed that the -1131T>C and 56C>G SNPs were significantly associated with higher plasma TG concentrations in both men and women. For RLP and lipoprotein subclasses, we observed gender-specific association for the -1131T>C and 56C>G SNPs. Female carriers of the -1131C allele had higher RLP concentrations, whereas in males, significant associations for RLPs were observed for the 56G allele. Moreover, haplotype analyses confirmed these findings and revealed that the 22122 and 11211 haplotypes exhibited different associations with HDL cholesterol concentrations. In women, the -1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03-3.34; P = 0.04), in agreement with the association of this SNP with higher RLPs.

Adult↗

Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population.

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.

Adult↗

The metabolic syndrome: a crossroad for genotype-phenotype associations in atherosclerosis.

The metabolic syndrome comprises a set of metabolic and physiologic risk factors associated with elevated cardiovascular disease risk. The expression of each one of its major factors (hypertriglyceridemia, low high-density lipoprotein cholesterol levels, hypertension, abdominal obesity, and insulin resistance) has been found to be the result of complex interactions between genetic and environmental factors. Moreover, obesity may play a major role in triggering the metabolic syndrome by interacting with genetic variants at candidate genes for dyslipidemia, hypertension, and insulin resistance. In support of this hypothesis, several studies at multiple candidate genes have already demonstrated the significance of these interactions; however, the data and their reliability are still very limited, and in many cases replication studies are still lacking in the literature. Therefore, more studies with better epidemiologic design and standardized adiposity measures are needed to estimate the contribution of body weight and fat distribution to the genetic predisposition to the metabolic syndrome, which is the most common cardiovascular disease risk factor in industrialized societies.

Adult↗

Gender-specific association of a perilipin gene haplotype with obesity risk in a white population.

OBJECTIVE: Perilipin is a class of protein-coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single-nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. RESEARCH METHODS AND PROCEDURES: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI > or = 30 kg/m(2). RESULTS: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. DISCUSSION: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.

Adipose Tissue↗

Nutritional genomics.

Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutrigenetics will provide the basis for personalized dietary recommendations based on the individual's genetic make up. This approach has been used for decades for certain monogenic diseases; however, the challenge is to implement a similar concept for common multifactorial disorders and to develop tools to detect genetic predisposition and to prevent common disorders decades before their manifestation. The preliminary results involving gene-diet interactions for cardiovascular diseases and cancer are promising, but mostly inconclusive. Success in this area will require the integration of different disciplines and investigators working on large population studies designed to adequately investigate gene-environment interactions. Despite the current difficulties, preliminary evidence strongly suggests that the concept should work and that we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes; nutrition will be the cornerstone of this endeavor.

Genetic Diseases, Inborn↗

Influence of plasma and erythrocyte factors on red blood cell aggregation in survivors of acute myocardial infarction.

Increased erythrocyte aggregation (EA) has been observed in patients with ischaemic heart disease (IHD), although most of these studies have been performed in the acute phase when reactant proteins may account for this increase. Little is known about the role played by the erythrocyte itself in this aggregation process. To ascertain the contribution of both plasma and erythrocyte factors to EA in IHD, we investigated the following parameters in 78 survivors of acute myocardial infarction (AMI) and in a well-matched control group of 98 subjects: EA, glucose, total cholesterol (T-Chol), low-density lipoprotein-cholesterol (LDL-Chol), high-density lipoprotein-cholesterol (HDL-Chol), triglycerides, apolipoproteins A(1) and B, protein and functional fibrinogen, plasma sialic acid, membrane sialic acid, and the cholesterol and phospholipid content of the erythrocyte membrane. AMI survivors showed higher glucose (p<0.001), a borderline increase in triglycerides (p = 0.043), and a statistical decrease in Apo A(1) (p= 0.003) relative to controls. EA, functional fibrinogen, and plasma sialic acid were statistically higher in AMI survivors than in controls (p= 0.001; p<0.001; p= 0.011, respectively). Membrane sialic acid content was statistically lower in AMI patients than in controls (p= 0.026). No differences were observed in either membrane cholesterol or phospholipids. Multivariate logistic regression analysis, in which EA was dichotomized as higher or lower than 8.7, demonstrated that triglyceride levels higher than 175 mg/dL (OR= 7.7, p= 0.001) and functional fibrinogen levels higher than 320 mg/dL (OR= 3.7, p= 0.004) were independently associated with a greater risk of erythrocyte hyperaggregability. Our results suggest that plasma lipids, predominantly triglycerides, and fibrinogen may not only enhance the development of ischaemic events by their recognized atherogenic mechanisms, but also by increasing EA.

Adult↗

Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke.

The association between factor V Leiden (FVL) and prothrombin G20210A (PT 20210) mutations and ischemic stroke remains controversial, particularly in young adults with cryptogenic stroke. Prevalence of FVL (4.1%) and PT 20210 (8.2%) mutations was assessed in 49 patients under 50 years with cryptogenic stroke and compared with controls. Odd ratio (OR) for cryptogenic stroke was 2.62 (95% CI, 0.49-13.95) for FVL and 3.75 (95% CI, 1.05-13.34) for PT 20210 and 3.28 (95% CI, 1,17-9.20) for some recognized genetic thrombophilic defect. Moreover, the OR for cryptogenic stroke in young women using oral contraceptives (OC) was 3.59 (95% CI, 1.28-10.5). When some genetic thrombophilic defect was associated with OC, the OR was much higher (OR: 14.27; 95% CI, 0.66-309.99). Our results suggest that in the Mediterranean populations the PT 20210 mutation, but not FV Leiden, is a risk factor for cryptogenic stroke in young adults. OC use is also a significant risk factor for cryptogenic stroke, which is increased in women with some genetic thrombotic risk factor.

Adolescent↗

Incidence of post-thrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis.

Post-thrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). However, neither the incidence nor the moment of PTS appearance are known. The main reason are the criteria used to define PTS, the characteristics of the patients, the study design and the time of follow-up. Our aims were to estimate the early incidence of PTS and its associated factors in a cohort of carefully defined DVT patients. 135 patients with a previous episode of acute idiopathic, phlebographically confirmed DVT, in the lower limbs, were followed up over 12 months. Phlebography was then repeated to determine the appearance of PTS. In addition, we used a validated clinical scale in order to assess the correlation between the clinical and phlebographical diagnosis of the PTS. This scale was applied at 6 and 12 months. The incidence of phlebographically confirmed PTS within the first year was 56.3% for the isolated PTS and 5.9% for PTS plus recurrent DVT, regardless of age, sex, platelet count, INR, or anticoagulation. None of these patients could be diagnosed as having PTS using the clinical validated scale. However, those patients with phlebographically diagnosed PTS had a higher clinical score than those without (P=0.012). The only factor related to a higher risk of developing a PTS was the localization of the DVT, subjects with both proximal and distal DVT having the highest incidence (P=0.001). In conclusion, although patients had appropriate anticoagulation, early incidence of PTS was very high, thus making it necessary to develop better diagnostic methods in order to evaluate the PTS impact.

Adult↗

Rheological profile in severe and morbid obesity. Preliminary results.

The association of hemorheological alterations with morbid obesity remains a question of debate. In order to ascertain whether morbid obese subjects show certain hemorheological alterations which might be involved in the higher thrombotic risk which characterizes these subjects, we determine glucose, plasma lipids, apolipoproteins, fibrinogen, hematocrit, blood viscosity (Brookfield DVIII viscosimeter), both at native and corrected hematocrit of 45%, plasma viscosity (Fresenius capillary viscosimeter), erythrocyte aggregation (Myrenne aggregometer), both at stasis and at 3 s(-1) at 45% hematocrit and erythrocyte indexes in 41 morbid obese subjects (32 female, 9 male aged 33+/-10 years), and in a well matched non-obese control group (40 female, 15 male, aged 32+/-10 years). Mean BMI in the morbid obese group was 44.9+/-6.7 kg/m2 vs 23.5+/-4.8 kg/m2 in the control group (p<0.001). Morbid obese subjects when compared with the control group showed a statistically higher glucose level (p<0.001), LDL-cholesterol (p=0.019), triglycerides (p<0.001), apoB (p=0.019), apoB/A1 (p<0.001), fibrinogen (p<0.001), erythrocyte aggregation (p<0.001), and a statistically lower HDL-cholesterol (p<0.001). No differences between both groups were observed regarding total-cholesterol, plasma viscosity, blood viscosity and hematocrit (p=0.109; p=0.690; p=0.510; p=0.950), respectively. After the adjustment for BMI, differences in glucose, LDL-cholesterol, triglycerides, apoB, apoB/A1, and erythrocyte aggregation did not reach the statistical significance, and differences in fibrinogen were borderline significant (p=0.051), showing a direct effect of BMI on the detected differences between obese and non-obese. Our results suggest that in morbid obese subjects the increased fibrinogen levels and the altered lipid profile associated with their higher BMI, could in addition to its known mechanisms on haemostasis, favour both venous and arterial thrombotic events by enhancing erythrocyte aggregation.

Adult↗

Effect of a hypocaloric diet on lipids and rheological profile in subjects with severe and morbid obesity. A follow-up study.

Discrepant results have been published regarding modifications of rheological parameters in obese subjects after a low caloric diet (LCD). In order to ascertain whether a decrease in BMI associated to a LCD, is accompanied by changes in the hemorheological parameters, we determined in 41 morbid obese subjects (32 female, 9 male aged 33+/-10 years) BMI, glucose, plasmatic lipids and apolipoproteins, fibrinogen, blood viscosity (Brookfield viscosimeter), plasma viscosity (Fresenius capillary viscosimeter), erythrocyte aggregation (Myrenne aggregometer), hematocrit and erythrocyte indexes, before starting on a LCD and 1 and 3 months after. During the first month obese subjects received a very low caloric diet (VLCD) (Modifast) providing 458 kcal per day. The second and third month they received a LCD providing 1500 kcal/day for men and 1200 kcal/day for women. One month after starting on a VLCD, a statistical significant decrease in glucose (p<0.001), Total-cholesterol (p<0.001), LDL-cholesterol (p<0.001), triglycerides (p=0.012), apoB (p<0.001) and erythrocyte aggregation (p<0.001) were observed together with a concomitant decrease in BMI (p<0.001). The expected decrease in HDL-cholesterol associated with a low fat diet was also noted in these individuals. No changes in fibrinogen, hematocrit, blood viscosity or plasma viscosity were observed. At 3 months only a slight increase in BMI was observed regarding the one month period, glucose being the only parameter which remained statistically lower. All the other significant parameters returned to their basal values at 3 months. VLCD (Modifast) is associated to a significant decrease in BMI with the corresponding improvement in glucose, lipids and erythrocyte aggregation at one month. However a LCD alone does not produce a further decrease in weight and both lipids and erythrocyte aggregation return to the basal situation at three months.

Body Mass Index↗

Influence of plasmatic lipids on the hemorheological profile in healthy adults.

Some hemorheological parameters constitute risk factors for ischemic cardiovascular events. Most of these hemorheological factors are determined by the erythrocyte intrinsic properties and the high molecular weight plasmatic proteins, especially fibrinogen. The contribution of the plasmatic lipids to hemorheological factors is not well established. With this aim we determined hemorheological parameters in 112 healthy volunteers (62 males, 50 females) aged 35+/-10 years, range 19-54 years, members of our hospital staff. A complete set of rheological test was performed. Blood viscosity (BV) 230 sec(-1), plasma viscosity (PV), erythrocyte aggregation index (EAI), erythrocyte elongation index (EEI), hematocrit and fibrinogen. We also determined plasmatic lipids including total cholesterol (T-Ch) and its fractions (HDL-Ch, LDL-Ch, VLDL-Ch), triglycerides, lipoproteins (Apo B, Apo A(1), B/A(1)). Exclusion criteria were concomitant cardiovascular risk factors or any other associated pathology. Our results show a positive correlation between BV 230 sec(-1) and triglycerides (r=0.335) and negative with HDL-Ch (r=-0.451) (p=0.01), respectively; PV shows a positive correlation with T-Ch (r=0.297), LDL-Ch (r=0.298) and Apo B/A (r=0.290) (p=0.01). The EEI was negatively correlated with TG (p=0.05). Of all the rheological parameters evaluated, EAI is the factor which shows the highest significant correlation with plasmatic lipids: T-Ch (r=0.515), TG (r=0.303), LDL-Ch (r=0.507) and Apo B/A ratio (r=0.403); (p=0.01). These results suggest that plasmatic lipids contribute to modulate the blood rheological properties, slowing blood flow, favouring the development of atherothrombotics events, especially in stenotic areas or bifurcations in the vascular tree.

Adult↗