[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.RESEARCH DESIGN AND METHODSA randomized trial (two MedDiet intervention groups and a control group) on 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HR) for cardiovascular events.RESULTSThe TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36-6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49-1.87]; P = 0.892 for TT compared with CC).CONCLUSIONS
Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.
[Show abstract][Hide abstract] ABSTRACT: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood.
To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake.
Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed.
FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P = 0.001).
Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.
PLoS ONE 01/2012; 7(12):e52344. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population.
We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires.
The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated with greater BMI, following a co-dominant pattern (P = 0.009), whereas in the OHP this association was recessive (P = 0.004). Conversely, we did not find a significant association with BMI in the HCR group (P < 0.596). In the GP we found a significant interaction between the FTO SNP and education (P = 0.048). In the stratified analysis, no association of the FTO SNP with greater BMI in university subjects was detected (P = 0.786), whereas the association was observed in non-university subjects (P = 0.001). The FTO × education interaction (P = 0.020) was also observed in determining obesity risk in the GP. A-allele carriers had a greater risk of being obese only if they had no university education (OR: 1.56; 95%CI: 1.09-2.23 for TA and OR: 2.01; 95%CI: 1.27-3.26 for AA subjects). The interaction of the FTO with education remained significant even after adjustment for PA.
The association of the FTO SNP with greater BMI and obesity risk in the GP was strongly modulated by education.
[Show abstract][Hide abstract] ABSTRACT: The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 ± 4.2 vs. 30.6 ± 4.2 kg/m(2); P = 0.003) and lower waist circumference (101.1 ± 11.8 vs. 103.5 ± 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also significantly higher in T-allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.
[Show abstract][Hide abstract] ABSTRACT: The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location.
To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT.
We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd-Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls.
In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P =0.044). After adjusting for total cholesterol, differences disappeared (P =0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P =0.199), even after adjusting for age and total cholesterol (P =0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P =0.253) or with SVT subtypes (P =0.885). No association was found between HH (>15 μm) and the TT genotype in cases (P =0.404), controls (P =0.178), or in the different SVT subtypes (P =0.495).
Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.
European Journal Of Haematology 11/2010; 86(2):167-72. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were independently associated with higher HDL-C (P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically significant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors.
The Journal of Lipid Research 09/2010; 51(9):2798-807. · 4.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.
A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.
Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P<0.001), no protective effect of the B2 allele against CHD incidence was observed. Thus, in comparison with B1B1 subjects, the adjusted CHD risk of B1B2 was OR: 1.00, 95% CI: 0.80-1.26; P=0.982, and that of B2B2 was OR: 1.16, 95% CI: 0.84-1.61; P=0.374. These results did not change after adjustment for HDL-C. No significant interaction between alcohol consumption and the CETP-TaqIB polymorphism in determining HDL-C was found. However, a different effect of this polymorphism on CHD risk in drinkers and non-drinkers was observed. In non-drinkers, the B2B2 genotype was associated with a non-significant lower CHD risk, whereas in drinkers it was associated with a greater risk (OR: 1.55, 95% CI: 1.05-2.29; P=0.026). We also observed that in diabetics (11% cases and 7.4% controls), the B2 allele was significantly associated with higher CHD risk.
In this Mediterranean population, the CETP-TaqIB polymorphism was not associated with a lower CHD incidence, and its effect was modulated by alcohol and possibly by diabetes.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study, a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk. The FFQ was administered twice (FFQ1 and FFQ2) to explore reproducibility at 1 year. Four 3 d dietary records (DR) were used as reference to explore validity; participants therefore recorded their food intake over 12 d in the course of 1 year. The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR. A total of 158 men and women (aged 55-80 years) were asked not to modify their dietary habits during the study period. Reproducibility for food groups, energy and nutrient intake, explored by the Pearson correlation coefficient (r) ranged 0.50-0.82, and the intraclass correlation coefficient (ICC) ranged from 0.63 to 0.90. The FFQ2 tended to report higher energy and nutrient intake than the DR. The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged (r) from 0.24 to 0.72, while the range of the ICC was between 0.40 and 0.84. With regard to food groups, 68-83 % of individuals were in the same or adjacent quintile in both methods, a figure which decreased to 55-75 % for energy and nutrient intake. We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospective studies.
The British journal of nutrition 06/2010; 103(12):1808-16. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Coffee and tea consumption recommendations for a healthy diet have been changing in recent years as it has increased the level of evidence on their benefits has increased. Objective: To know the frequency of coffee and tea consumption of in a high cardiovascular risk Mediterranean population (CVR) and to analyze whether there are differences between the consumption of these drinks by cardiovascular risk factors. Methods: A cross-sectional study was carried out on 945 people (340 males, 605 females) (67.4 ± 6.2 years old) with high CVR recruited in primary care centres of Valencia, included in the PREDIMED study. Coffee and tea consumption has been determined through a validated questionnaire. We analyzed biochemical, clinicaland anthropometric variables by standard methods. Results: Tea consumption is very low in this Mediterranean population (0,4 ± 1,6 cups/weeks). By contrast, coffee consumption averaged nearly one cup per day (6,5 ± 5,2 cups/weeks). Hypertensive patients showed a lower overall consumption of coffee than in non-hypertensive patients (6,6 ± 5,1 vs 7,3 ± 5,9; P = 0,023 respectively). These differences were greatest when caffeinated coffee consumption is analyzed (2.9 ± 4.5 vs 4 3 ± 5.3, P < 0001). Moreover, diabetics consumed significantly less coffee and tea than non-diabetics (P = 0,015 and P = 0,022 respectively), these differences being greater for caffeinatedcoffee (P < 0,025). Conclusions: In conclusion, in this high cardiovascular risk Mediterranean population a coffee consumption pattern, based on traditional recommendations, is observed, that as a result of new scientific evidence should be update.
Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 06/2010; 25(3):388-393. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coffee and tea consumption recommendations for a healthy diet have been changing in recent years as it has increased the level of evidence on their benefits has increased.
To know the frequency of coffee and tea consumption of in a high cardiovascular risk Mediterranean population (CVR) and to analyze whether there are differences between the consumption of these drinks by cardiovascular risk factors.
A cross-sectional study was carried out on 945 people (340 males, 605 females) (67.4+/-6.2 years old) with high CVR recruited in primary care centres of Valencia, included in the PREDIMED study. Coffee and tea consumption has been determined through a validated questionnaire. We analyzed biochemical, clinical and anthropometric variables by standard methods.
Tea consumption is very low in this Mediterranean population (0.4+/-1.6 cups/weeks). By contrast, coffee consumption averaged nearly one cup per day (6.5+/-5.2 cups/weeks). Hypertensive patients showed a lower overall consumption of coffee than in non-hypertensive patients (6.6+/-5.1 vs 7.3+/-5.9; P=0.023 respectively). These differences were greatest when caffeinated coffee consumption is analyzed (2.9+/-4.5 vs 4.3+/-5.3, P<0001). Moreover, diabetics consumed significantly less coffee and tea than non-diabetics (P=0.015 and P=0.022 respectively), these differences being greater for caffeinated coffee (P<0.025).
In conclusion, in this high cardiovascular risk Mediterranean population a coffee consumption pattern, based on traditional recommendations, is observed, that as a result of new scientific evidence should be update.
Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 01/2010; 25(3):388-93. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7'8'-dihydro-2'-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were significantly higher while catalase and glutathione peroxidase activities were significantly lower in high cardiovascular risk participants than in controls. Statistically significant differences were obtained after additional multivariate control for sex, age, obesity, diabetes, lipids and medications. Among the main cardiovascular risk factors, hypertension was the strongest determinant of oxidative stress in high risk subjects studied at a primary prevention stage.
Free Radical Research 12/2009; 43(12):1179-86. · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 +/- 4.82 in GG vs. 4.74 +/- 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 +/- 114.8 in GG vs. 243.0 +/- 107.1 microg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.
Journal of Nutrition 01/2009; 139(1):128-34. · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Serum adiponectin concentrations have been inversely associated with abdominal obesity, a more favorable lipid profile, and less insulin resistance. Nevertheless, recent studies in the population at high cardiovascular risk, especially that with altered renal function, show that high adiponectin concentrations are an unfavorable indicator. The aim of this study was to analyze the association of adiponectinemia with anthropometric, biochemical and blood pressure parameters in patients with high cardiovascular risk.
Patients and methods
We studied 185 patients (133 women and 52 men), participating in the PREDIMED study (mean age 65.5 ± 4.3 years). Clinical, anthropometric, biochemical and blood pressure data, as well as adiponectinemia, were analyzed.
The body mass index was slightly higher in women than in men (31.1 ± 4.3 kg/m2 versus 29.4 ± 4.0 kg/m2; p = 0.01). The prevalence of diabetes was 42.2% and was higher in men (61.5%) than in women (34.6%). Adiponectin concentrations were higher in women than in men (11.0 ± 5.2 versus 6.9 ± 3.3 μg/mL; p < 0.001). After adjustment for sex, mean adiponectin concentrations were higher in nondiabetic than in diabetic participants (10.3 ± 0.5 versus 7.5 ± 0.5; p < 0.001). Positive correlations between adiponectin and high-density lipoprotein cholesterol were obtained (r = 0.36; p < 0.001). Negative correlations with plasma triglycerides (r = −0.28; p < 0.001), glycemia (r = −0,28; p < 0.001) and plasma creatinine (r = −0.28; p = 0.007) were found. No association was found between adiponectinemia and systolic or diastolic blood pressure.
In the population studied with high cardiovascular risk, the correlations between adiponectinemia and anthropometric parameters and blood pressure were less clear than those in the general population. However, adiponectin concentrations were lower in diabetics and were inversely correlated with creatinine levels.
Clínica e Investigación en Arteriosclerosis. 08/2007; 19(4).
[Show abstract][Hide abstract] ABSTRACT: The final phenotype of patients with cystinuria depends on the absence or molecular defect, more or less acute, of the transport of cystine and dibasic aminoacids, and, also on environmental factors. The objective of this work is to study the effect of the modulation of some environmental factors (urinary pH, intake of liquids, pharmacological treatment and, specially, diet) on the final phenotype of the patient with cystinuria.
We study 45 patients with cystinuria (25 men and 20 women), 42 relatives (15 men and 27 women) and 90 unrelated controls. Anthropometric, clinical (personal and familiar history of urinary infections, colics and calculi expulsion), biochemical (microscopy analysis of urine and urinary aminoacids cuantification) and life style (diet and medical treatment) variables were obtained. Statistical analysis was performed using tests to compare means and frequencies and, also, logistic regression and multivariate analysis.
Of the 45 patients with cystinuria, only 20% showed cystine cristalls in urine, the rest of the phenotypical manifestations of cystinuria were found with the same prevalence as in relatives and in the control group. 50% of the patients did not undergo any therapeutic intervention; of these, only 50% were effective. In patients with cystinuria, the presence of cystine cristalls was associated with a diet rich in meats and poor in milk products (p < 0.05). Meat consumption also tend to associate with a higher risk of urinary infections, meanwhile the stone expulsion showed a negative tendance with a diet rich in phytate. The elevate consumption of oranges and mandarins was the variable of the diet which was more associated with urinary aminoacids concentrations, specially with lower levels of lysine and arginine (p < 0.05).
Some components of the diet, in addition to standard treatment, modulate the phenotypical manifestations of cystinuria.
Archivos españoles de urología 04/2007; 60(2):109-18.
[Show abstract][Hide abstract] ABSTRACT: Objetivo: El fenotipo final del paciente con cistinuria depende, por una parte, de la ausencia o defecto molecular más o menos grave en el transporte de cistina y aminoácidos dibásicos; y por otra parte también de factores ambientales. El objetivo del presente estudio es conocer el efecto de la modulación de diversos factores ambientales (pH urinario, ingesta de líquido, tratamiento farmacológico y en especial la dieta) sobre el fenotipo final del paciente con cistinuria. Métodos: Se estudiaron 45 sujetos diagnosticados como pacientes con cistinuria (25 hombres y 20 mujeres), 42 individuos pertenecientes al árbol genealógico de estos pacientes con cistinuria (15 hombres y 27 mujeres) y 90 controles. Se obtuvieron datos antropométricos, clínicos (antecedentes personales y familiares de infecciones urinarias, cólicos, expulsión de cálculos y problemas renales), bioquímicos (análisis microscópico de orina y cuantificación de aminoácidos en orina) y estilo de vida (dieta y tratamiento recibido). El estudio estadístico incluyó, además de pruebas de comparación de frecuencias y de medias, regresión logística y análisis multivariante. Resultados: De los 45 pacientes con cistinuria, sólo el 20% presentaban cristales de cistina en orina; el resto de manifestaciones fenotípicas de la enfermedad, se encontraron con la misma prevalencia que en el grupo de familiares y el grupo control. El 50% de los pacientes no estaban siguiendo ninguna pauta terapéutica, y de estos, solo en el 50% era efectivo. En pacientes con cistinuria, la presencia de cristales de cistina se asoció a una dieta rica en carnes y baja en productos lácteos (pConclusiones: Diversos componentes de la dieta, además del tratamiento estándar, modulan las manifestaciones fenotípicas de la enfermedad.
Archivos españoles de urología 03/2007; 60(2):109-118.
[Show abstract][Hide abstract] ABSTRACT: Plasma viscosity (PV) constitutes an independent important predictor of initial and recurrent cardiac events and mortality. It has been suggested that there is a geographical variation in PV values related to coronary event rates. Little information exists regarding PV in Spain. Therefore, our objective was to determine PV in a large sample of randomly selected subjects from the Spanish population and to study which demographic or cardiovascular risk factors (CVRF) influence levels of PV in this population.
1277 subjects (503 males, 774 females) aged 43+/-14 years (range: 20-70) were randomly selected from an Eastern Spanish population. These subjects were free of cardiovascular diseases and other major diseases. PV was measured at 37 degrees C by means of the Fresenius GmbH plasma viscosimeter. In addition, total cholesterol, triglycerides, glucose and fibrinogen were measured.
In the crude analysis, no differences in PV were observed regarding gender (males: 1.235+/-0.061 cP; females: 1.236+/-0.059 cP, P=0.952). Women older than 50 years showed higher PV:1.248+/-0.057 cP than those aged less than 50 years: 1.232+/-0.059 cP, P=0.001. No differences in PV by age groups were observed in men (P=0.842). Furthermore, we evaluated the prevalence of the following CVRF: hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, tobacco smoking, obesity, and high fibrinogen levels. Prevalence of these factors was: 28%, 4.3%, 8%, 2.3%, 33%, 8.8% and 15% respectively. As some of these CVRF were correlated with PV levels, we carried out a multivariate analysis to adjust PV levels for the potential confounding effect of each one of these factors. After multivariate adjustment, PV was positively associated with high fibrinogen (>320 mg/dL) levels in both men and women (P<0.001). In addition, in women, but not in men, PV levels were independently associated with obesity (P<0.001) and hypertriglyceridemia (P=0.01). After the multivariate adjustment, the association between PV and age older than 50 in women did not remain statistically significant, revealing a confusing effect of the CVRF in the crude analysis.
Thrombosis Research 01/2007; 120(4):489-95. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the presence of the most prevalent mutation in the SLC7A9 gene in families of the Mediterranean Spanish population and their association with clinical phenotypes.
Twenty cystinuria families were studied (6 type I, 12 non type I, and 2 unknown type), including 48 cystinuria patients and 44 relatives. DNA was isolated and molecular analysis of 13 variations (P52L, N58_G79del22, G63R, G105R, T123M, V170M, A182T, V188M, c.614dupA, G259R, L283F, A316V and R333W) in the SLC7A9 gene was undertaken. Association studies between these mutations and urinary aminoacid concentrations, stones, urinary infections, colics and other clinical traits were carried out.
Of the 13 investigated mutations, the most prevalent mutation in cystinuria patients was c.614dupA (17.1%), which was found in 13 patients in heterozygous state (17.1%) and in 2 relatives, all of them belonging to 4 non type I families. Mutations G105R (9.2%), T123M (3.9%) and N58_G79del22 (2.6%) were detected only in non type I cystinuria patients. Meanwhile, a R333W carrier allele was found in a patient of a unknown family, and a G105R allele in a relative of a non type I family. No mutation was found in type I families and no patients with mutations in both SLC3A1 and SLC7A9 genes were found in any family.
Although we have not carried out the whole screening of SLC7A9 gene, the detection rate of variations in SLC7A9 gene suggests a greater impact of this gene in the etiology of cystinuria in our population than variations in the previously screened SLC3A1 gene. The wide variation of phenotypical traits in subjects of families with the same mutations suggests that further investigation of other genetic and/or environmental factors should be carried out.