Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk population: modulation by the Mediterranean diet.

The SNP rs1260326 (P446L) and rs1799884 (-30G>A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concentrations (PP: 1.34 (SD 0.05) mmol/l v. PL+LL: 1.54 (SD 0.03) mmol/l; P= 0.014) and LL carriers had lower glucose concentrations (PL+PP: 6.85 (SD 0.08) mmol/l v. LL: 6.40 (SD 0.16) mmol/l; P= 0.032) after multivariate adjustment. Conversely, homozygous subjects for the variant allele (A) in the GCK gene had significantly lower TAG (GG+GA: 1.48 (SD 0.03) mmol/l v. AA: 1.17 (SD 0.18) mmol/l; P= 0.033) and a higher risk of diabetes (OR 3.3, 95 % CI 1.2, 9.2). Combined effects for both SNP increased TAG concentrations by 37 % (P= 0.033). Adherence to the MD modulated the effects of GCKR polymorphism on TAG: subjects with genetic risk had lower TAG (L-allele carriers; PP: 1.48 (SD 0.14) mmol/l v. PL+LL: 1.51 (SD 0.08) mmol/l; P= 0.917) compared with those with a higher adherence. Analysis of the joint effects of the GCKR and individual food items identified significant associations (olive oil (P= 0.035), vegetables (P= 0.012), red meat (P= 0.017), butter (P= 0.039), sweetened carbonated beverages (P= 0.036) and nuts (P= 0.038)). In conclusion, we found that rs1260326 (GCKR) is significantly associated with higher TAG concentrations, but is modulated by adherence to the MD.

Assessment of the Health Status of Spanish Schoolchildren Based on Nutrimetry, Lifestyle and Intestinal Parasites.

Malnutrition in Spanish schoolchildren, and its relationship with lifestyles, has been studied, but Nutrimetry (a nutritional status indicator), and data on intestinal parasitism and its risk factors, have never before been taken into account. A total of 206 children aged 3-11 years, from two schools in the Valencian Community, participated. Demographic characteristics, diet, lifestyles, behavioural habits and anthropometric (weight, height) and coproparasitological data were collected. Nutrimetry was used to analyse nutritional status. Statistical analyses were performed to ascertain associations between lifestyle, selected parasite species and nutritional status. Multivariate logistic regression analysis was used to assess the strength of the association of the suspected risk factors with the presence of intestinal parasitism. The prevalence of overweight was 32.6%. A total of 43.9% had a high adherence to the Mediterranean Diet, for which mean daily intake was 2428.7 kcal. Intestinal parasitism was identified in 49.5% of the children (Giardia duodenalis: 28.6%). The source of drinking water was found to be a risk factor for intestinal parasitism. No positive association between the variables analysed and nutritional status could be confirmed. Nutrimetry is a good indicator for a complete analysis of nutritional status. It highlights the prevalence of overweight. Intestinal parasitism was identified in almost half of the participants and is a variable that should not be underestimated.

Prevalence and associated risk factors of intestinal parasites among schoolchildren in Ecuador, with emphasis on the molecular diversity of Giardia duodenalis, Blastocystis sp. and Enterocytozoon bieneusi.

BACKGROUND: Intestinal helminths, including Soil-Transmitted Helminth (STH), and Gastrointestinal Protist (GP) infections are major contributors to the global burden of disease, particularly in low-income countries such Ecuador. Their epidemiology in these settings is largely unknown. METHODOLOGY: This prospective cross-sectional study investigates the carriage of intestinal helminths, including STH, and GP in asymptomatic schoolchildren (3-11 years) in the Chimborazo and Guayas provinces, Ecuador. Single stool samples (n = 372) and epidemiological questionnaires on demographics and potential risk factors were collected from participating schoolchildren. Conventional microscopy examination was used as screening method, and molecular (PCR and Sanger sequencing) assays were used to further investigate the epidemiology of some GP. A multivariate logistic regression analysis was used to evaluate the strength of the association of suspected risk factors with the presence of helminths and GP. PRINCIPAL FINDINGS: At least one intestinal parasite species was observed by microscopy in 63.2% (235/372) of the participating schoolchildren. Enterobius vermicularis (16.7%, 62/372; 95% CI: 13.0-20.9) and Blastocystis sp. (39.2%, 146/372; 95% CI: 34.2-44.2) were the most prevalent among helminths and GP, respectively. Assemblages A (50.0%), B (37.5%) and A+B (12.5%) were detected within Giardia duodenalis and ST3 (28.6%), ST1 and ST2 (26.2% each), and ST4 (14.3%) within Blastocystis sp. Three genotypes, two known (A: 66.7%; KB-1: 16.7%) and a novel (HhEcEb1, 16.7%) were identified within Enterocytozoon bieneusi. Municipality of origin, household overcrowding, and poor sanitation and personal hygiene habits were risk factors for childhood intestinal parasites colonization. CONCLUSIONS/SIGNIFICANCE: Despite massive government drug administration programs, STH and GP infection remain a public health concern in paediatric populations living in poor-resource settings. Molecular analytical methods are required to better understand the epidemiology of these intestinal parasites. This study provides novel information on the occurrence of Blastocystis sp. and E. bieneusi genetic variants circulating in Ecuadorian human populations.

The antioxidant status response to low-fat and walnut paste-enriched meat differs in volunteers at high cardiovascular Risk carrying different PON-1 polymorphisms.

BACKGROUND: Cardiovascular risk largely depends on diet, antioxidant status, and gene polymorphisms. Low-fat meat (CM) and walnut-enriched meat (WM) products may exert potential beneficial health effects with respect to conventional meat products. OBJECTIVE: To compare the effects of consuming WM vs CM on reduced and oxidized glutathione, lipoperoxides, α- and γ-tocopherol levels, and paraoxonase (PON-1), catalase (CAT), and superoxide dismutase (SOD) activities in 22 volunteers (mean age 54.8 years and body mass index 29.6 kg/m(2)) at high cardiovascular risk carrying different PON-1 192/55 polymorphisms. DESIGN: The study was a 5-week nonblinded, randomized, crossover, controlled trial. RESULTS: In general term, WM vs CM improved the volunteers' antioxidant status, with several result modifications occurring after the WM period. CM consumption increased oxidized glutathione and decreased PON-1 activity (at least p < 0.05). When WM vs CM effects were compared, SOD, CAT, and PON-1 enzyme activities increased (at least p < 0.05) in PON-1 192QQ carriers. γ-tocopherol levels and SOD and PON-1 activities increased in PON-1 192QR+RR carriers besides the significant decrease of lipoperoxide levels. In PON-1 55LM+MM carriers, the intervention increased significantly all the investigated enzyme activities and glutathione levels, whereas PON-1 55LL carriers increased their PON-1 activities. CONCLUSIONS: WM consumption should be preferred to CM. The intake of WM vs CM increased PON-1 but the effect upon other antioxidant enzymes and substrates varied depending on the individual's PON-1 polymorphism. PON-1 192QR+RR carriers appear the targets for WM consumption as they increased enzyme activities and γ-tocopherol levels and decreased lipoperoxides.

Evaluation of School Children Nutritional Status in Ecuador Using Nutrimetry: A Proposal of an Education Protocol to Address the Determinants of Malnutrition.

The education sector is a cornerstone in the battle against malnutrition in children. However, there are still no consolidated protocols that outline strategies for how nutrition programs in low- and middle-income countries can be delivered through the education sector. Establishing the correct community diagnosis is essential prior to the elaboration of an intervention plan for a school population that takes into account more than just traditional variables related to the nutritional status. A total of 574 boys and girls aged 3-11 years from three educational institutions in different municipalities in Ecuador participated in the study. Sociodemographic, anthropometric (weight and height) and coproparasitological data were obtained. Nutrimetry, which is a combination of two classical anthropometrics indicators, was used for the analysis of the nutritional status, and the indicators' frequencies varied among the schools. In order to improve the nutritional status of children, we proposed a framework mainly focusing on establishing alliances with the education sector and taking into account gender equality; respect for the environment; and the customs, beliefs and traditions of each population. The results obtained from the analyses of other variables demonstrated the importance of an adequate diagnosis prior to any type of intervention at the nutritional level, since characteristics could vary by local area and have an impact on the successfulness of the intervention.

Effects of APOA5 S19W polymorphism on growth, insulin sensitivity and lipoproteins in normoweight neonates.

Apolipoprotein (Apo) A5 is a protein involved in the activation of lipoprotein lipase (LPL) and the metabolism of triglyceride (TG)-rich lipoproteins. LPL plays a major role in the metabolism of TG-rich lipoproteins, and placental LPL activity is known to correlate positively with foetal fat deposition and size. We examine the association between the common APOA5 S19W polymorphism and neonatal anthropometrical measurements, lipoprotein and hormone concentrations, and insulin sensitivity in 58 normal weight Caucasian newborns from the Mérida cohort. Neonates with the W allele displayed lower BMI (P < 0.001), ponderal index (P < 0.001), birth weight (P < 0.01), insulin levels (P < 0.05), the insulin/cortisol ratio (P < 0.05), HOMA-R (P < 0.05) and Apo B values (P < 0.01), but higher oxidised LDL (LDLox) values and a higher LDLox/low-density lipoprotein (LDL) ratio (both P < 0.05) than S-homozygous newborns. The APOA5 S19W polymorphism was associated with foetal growth as well as with glucose and lipoprotein metabolism in the neonates. Concurrence of the S19W polymorphism in neonates and their mothers did not affect neonatal lipid and lipoprotein concentrations but was associated with impaired foetal growth. Specifically, W allele carriers displayed a higher degree of LDL oxidation and lower body weight, plasma insulin values, insulin/cortisol ratio and Apo B concentrations than homozygotes for the common S allele. In conclusion, these findings suggest that the W allele carriers received a less optimal nutrition during gestation and that their lipoprotein antioxidant status was inferior to that of their homozygous S allele counterparts.

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population.

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 rs1466113 polymorphism in the somatostatin receptor 2 gene is associated with obesity and food intake in a Mediterranean population.

BACKGROUND: A genome-wide association study identified rs1466113 (G>C) in the somatostatin receptor 2 (SSTR2) gene as one of the polymorphisms most significantly associated with body mass index (BMI). As replication is required, we examined the association between this polymorphism and anthropometric variables and food intake in a Mediterranean population. METHODS: We studied 945 high cardiovascular-risk subjects (340 men and 605 women) aged 67 ± 6 years, participating in the PREDIMED-Valencia Study. Demographic, clinical, biochemical, dietary, genetic and anthropometric data were obtained. RESULTS: We found recessive effects for the association between this polymorphism and anthropometric variables. Homozygous subjects for the C allele had significantly lower BMI than G-allele carriers (29.9 ± 4.5 in CC vs. 31.0 ± 4.9 in GG + GC; p = 0.035). Likewise, odds ratio for obesity was lower in CC subjects in comparison with G-allele carriers, even after adjustment for potential confounders (odds ratio: 0.60, 95% confidence interval: 0.38-0.94; p = 0.028). We also found significant differences in food (meats, dairy products and legumes) and nutrient (protein) intakes between CC- and G-allele carriers. CONCLUSION: The rs1466113 polymorphism in the SSTR2 gene is associated with anthropometric variables in the Mediterranean population replicating previous results in the Framingham study. We also observed differences in food intake between genotypes.

Assessment of the Nutritional Status, Diet and Intestinal Parasites in Hosted Saharawi Children.

Since the early 1990s, Spanish humanitarian associations have welcomed Saharawi children from the refugee camps in Tindouf (Argelia). These children are the most affected by the lack of food, water, hygienic measures and health care. The main objective of this study was to analyze the anthropometric, nutritional and parasitological data of 38 Saharawi boys and girls (from 10 to 13 years old) under a holiday host program in the city of Valencia. Our results confirm that malnutrition and multiparasitism are highly frequent, so it is understood that living conditions in refugee camps continue to be precarious with a lack of proper hygiene and nutrition. Furthermore, biochemical alterations, lactose malabsorption and the risk of celiac disease, also detected in our study as a secondary objective, will complicate nutritional management and restoration of health. For this reason, sustainable feeding alternatives and interventions from a hygienic and nutritional point of view are proposed, emphasizing in an improvement in the education of parents and children.

The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population.

BACKGROUND: Apolipoprotein E (ApoE) locus has consistently shown a significant association with low-density lipoprotein cholesterol (LDL-C). However, its impact on high-density lipoprotein cholesterol (HDL-C) has been highly controversial suggesting that it may be context-dependent. We examined the gene-gene interaction between the common ApoE and the CETP polymorphisms in determining HDL-C concentrations in men and women from the general population. METHODS: 550 unrelated Caucasian subjects were randomly selected from a Mediterranean Region in Spain. Plasma lipids, anthropometric, clinical and lifestyle variables were measured. Common ApoE and CETP-TaqIB polymorphisms were determined. RESULTS: We have found a gene-gene interaction between and ApoE and the CETP loci in determining HDL-C concentrations. Thus, after adjustment for gender, age, body mass index, tobacco smoking, alcohol consumption, physical exercise and medication, carriers of the E4 allele had lower HDL-C concentrations [mean and (standard error): 40.1 (2.6) mg/dL] than E2 subjects [47.7 (3.2) mg/dL; p=0.019], and even lower than those of the E3 subjects [44.7 (1.4) mg/dL; p=0.042], only if they had the B1B1 genotype. However, mean HDL-C concentrations were higher among those with E4 allele carrying the B2 allele at the CETP gene locus [50.5 (2.3) mg/dL], and lower among E2 subjects carrying the B2 allele [45.5 (2.6) mg/dL]. This interaction was observed in both men and women. This gene-gene interaction remained statistically significant even after additional adjustment for triglycerides. CONCLUSIONS: The effect of the ApoE polymorphism on HDL-C concentrations depends on the CETP polymorphism, explaining some of the controversial results previously reported for this polymorphism.

[SLC7A9 gene variation: impact of 13 frequent mutations in the etiology of cystinuria in a Spanish Mediterranean population]. / Variaciones en el gen SLC7A9: impacto de trece mutaciones frecuentes en la etiología de la cistinuria en población mediterránea española.

BACKGROUND AND OBJECTIVE: 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. PATIENTS AND METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal and neonatal FTO rs9939609 polymorphism affect insulin sensitivity markers and lipoprotein profile at birth in appropriate-for-gestational-age term neonates.

The influence of maternal fat mass and obesity (FTO) gene polymorphism on neonatal insulin sensitivity/resistance biomarkers and lipoprotein profile has not been tested. The study aimed to assess the association between the FTO rs9939609 polymorphism in mother-neonate couples and neonatal anthropometrical measurements, insulin sensitivity/resistance, and lipid and lipoprotein concentrations at birth. Fifty-three term, appropriate-for-gestational-age, Caucasian newborns together with their respective mothers participated in a cross-sectional study. Sixty-six percent of mothers and neonates carried the A allele (being AA or AT). TT mothers gained less weight during pregnancy, but non-significant maternal gene influence was found for neonatal bodyweight, body mass index, or ponderal index. Neonates from AA + AT mothers showed lower glucose, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) but higher homeostatic model assessment insulin sensitivity (HOMA-IS) and homocysteine than neonates whose mothers were TT. AA + AT neonates had higher insulin and HOMA-IR than TT. The genotype neonatal × maternal association was tested in the following four groups of neonates: TT neonates × TT mothers (nTT × mTT), TT neonates × AA + AT mothers (nTT × mAA + AT), AA + AT neonates × TT mothers (nAA + AT × mTT), and AA + AT neonates × AA + AT mothers (nAA + AT × mAA + AT). Non-significant interactions between neonatal and maternal alleles were found for any parameter tested. However, maternal alleles affected significantly glucose, insulin, HOMA-IR, and homocysteine while neonatal alleles the arylesterase activity. Most significant differences were found between nATT + AA × mTT and nATT + AA × mAA + AT. Glycemia, insulinemia, and HOMA-IR were lower, while the Mediterranean diet adherence (MDA) was higher in the mAA + AT vs. mTT whose children were AA + AT. This dietary fact seems to counterbalance the potential negative effect on glucose homeostasis of the obesogenic A allele in neonates.

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.

[Effects of the apolipoprotein E polymorphism on plasma lipid levels and cardiovascular disease risk in a Mediterranean population]. / Efecto del polimorfismo de la apolipoproteína E en el perfil lipoproteico y riesgo cardiovascular en una población mediterránea.

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.

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet.

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate-low linkage disequilibrium (D' = 0.719; r (2) = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; P additive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; P recessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (P additive = 0.016, P recessive = 0.011), low-density lipoprotein cholesterol (P additive = 0.032, P recessive = 0.031) and triglycerides (P additive = 0.040, P recessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD.

Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.

BACKGROUND & AIMS: Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile. METHODS: Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention. RESULTS: Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention. CONCLUSIONS: These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages. www.isrctn.org: ISRCTN88720134.

Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method.

Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then applied to a clinical study with high cardiovascular risk subjects, after the moderate consumption of red wine (RW) or dealcoholized red wine (DRW) for 28 days. Up to 21 resveratrol metabolites, including those formed by gut and microbial metabolism, were identified in 24-h urine samples. Interestingly, after long-term consumption of RW and DRW, resveratrol metabolite concentration significantly increased in urine with no differences between the two interventions, indicating that bioavailability and biotransformation of resveratrol is not affected by the alcoholic matrix of wine. In summary, we established a sensitive analytical assay for the quantification of a wide resveratrol metabolic profile in human urine, also regarding gut microbial-derived metabolites, which may also be applied to blood and tissue samples. The resveratrol metabolic pattern might therefore act as an excellent marker for the efficacy of resveratrol in clinical and epidemiological studies for the study of the beneficial effects of grape product consumption. In this sense, having a more precise concentration value of all the resveratrol metabolites in target tissues would finally lead to a better interpretation of the obtained results.

Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial.

BACKGROUND: Few clinical studies have focused on the alcohol-independent cardiovascular effects of the phenolic compounds of red wine (RW). OBJECTIVE: We aimed to evaluate the effects of ethanol and phenolic compounds of RW on the expression of inflammatory biomarkers related to atherosclerosis in subjects at high risk of cardiovascular disease. DESIGN: Sixty-seven high-risk, male volunteers were included in a randomized, crossover consumption trial. After a washout period, all subjects received RW (30 g alcohol/d), the equivalent amount of dealcoholized red wine (DRW), or gin (30 g alcohol/d) for 4 wk. Before and after each intervention period, 7 cellular and 18 serum inflammatory biomarkers were evaluated. RESULTS: Alcohol increased IL-10 and decreased macrophage-derived chemokine concentrations, whereas the phenolic compounds of RW decreased serum concentrations of intercellular adhesion molecule-1, E-selectin, and IL-6 and inhibited the expression of lymphocyte function-associated antigen 1 in T lymphocytes and macrophage-1 receptor, Sialil-Lewis X, and C-C chemokine receptor type 2 expression in monocytes. Both ethanol and phenolic compounds of RW downregulated serum concentrations of CD40 antigen, CD40 ligand, IL-16, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1. CONCLUSION: The results suggest that the phenolic content of RW may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of RW may modulate soluble inflammatory mediators in high-risk patients. The trial was registered in the International Standard Randomized Controlled Trial Number Register at http://www.isrctn.org/ as ISRCTN88720134.

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population.

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.

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states.

BACKGROUND: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. OBJECTIVE: We investigated the combined effects of the GCKR rs780094C-->T, APOA5 -1131T-->C, and APOA5 56C-->G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. DESIGN: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7,730 men and women) and 2 intervention studies in US whites (n = 1,061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). RESULTS: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001). CONCLUSIONS: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment.