Interleukin-6 and tumor necrosis factor-alpha gene polymorphisms in chronic idiopathic urticaria

BackgroundThis study was performed to evaluate association of gene polymorphisms among proinflammatory cytokines and susceptibility to chronic idiopathic urticaria (CIU).MethodsNinety patients with prolonged urticaria more than 6 weeks were included as case group. Single nucleotide polymorphisms (SNPs) of IL-6 (G/C −174, G/A nt565) and TNF-α (G/A −308, G/A −238) were evaluated, using polymerase chain reaction (PCR); and the results were compared to the control group.ResultsG allele was significantly higher in the patients at locus of −238 of promoter of TNF-α gene (p < 0.001). Frequency of following genotypes were significantly lower in patients with CIU, compared to controls: AG at −308 and GA at −238 of TNF-α gene (p < 0.05 and p < 0.001, respectively), CG at −174 and GG at +565 of IL-6 gene (p < 0.05). Additionally, following genotypes were more common among patients with CIU: GG at −308 and −238 of TNF-α gene (p < 0.05 and p < 0.001, respectively), GG at −174 and GA at +565 of IL-6 gene (p < 0.05).ConclusionsPro-inflammatory cytokine gene polymorphisms can affect susceptibility to CIU. TNF-α promoter polymorphisms as well as IL-6 gene polymorphisms are associated with CIU.     

IL1B genetic variation and plasma C-reactive protein level among young adults: the CARDIA study

ObjectiveInterleukin-1B (IL1B) modulates C-reactive protein (CRP) expression. However, whether IL1B genetic variation is associated with CRP level is unknown. Further, obesity, a state of low-grade inflammation that influences cellular IL-1 functions may modify this association.Methods and resultsStudy participants (N = 3289), 48% blacks and 52% whites, had CRP level measurements at year 7 and year 15 examinations as part of the CARDIA study. Ten tag single nucleotide polymorphisms (SNPs) that characterize common IL1B gene variation were genotyped. In SNP analysis, no significant associations with either level or change in time CRP were observed after multiple testing adjustments. However, global ILIB gene variation was associated with year 7 to year 15 change in CRP (global nominal p = 0.004, multiple testing corrected p = 0.048) among obese blacks. Compared to the commonest haplotype, a common haplotype that includes the SNP rs1143642 was associated with greater increases in CRP from year 7 to year 15 among obese blacks and whites while another common haplotype that includes the SNP rs3917356 was associated with decreased change in CRP from year 7 to year 15 among obese blacks. The rare alleles of ILIB SNPs, SNP 7114 (rs1143642) and SNP 3298 (rs3917356), were associated with greater increases and decreases in CRP from year 7 to year 15 among blacks, respectively, compared to their common variants.ConclusionIL1B genetic variation may have a role in CRP level regulation and this association may be modified by obesity.     

The differences in the involvements of loci of promoter region and Ile50Val in interleukin-4 receptor α chain gene between atopic dermatitis and Japanese cedar pollinosis

BackgroundAtopic dermatitis (AD) and Japanese cedar pollinosis (JCP) are common chronically allergic diseases associated with the activation of T-helper 2 cells. Recent studies have shown that polymorphisms in the genes for IL-4 receptor α chain (IL4RA) may contribute to susceptibility of AD and JCP, although the differences in the involvements of loci of IL4RA gene between AD and JCP are unclear. In this study, we investigated the role of polymorphisms in IL-4RA gene in conferring susceptibility to the development of AD and/or JCP using a family analysis and an association analysis in a Japanese population.MethodsFive polymorphisms in the IL-4RA gene, C-3223 T, T-1914C, T-890C, Ile50Val and Glu375Ala, have been genotyped using PCR-based methods in 75 trios families, including 15 AD families, 30 JCP families, and 30 families with combination of AD and JCP in the family analysis. Forty-five AD, 60 JCP and 125 control children constituted the association study.ResultsThe transmission disequilibrium test showed that the allele of Ile50 was significantly transmitted to children with JCP alone (p < 0.05). Haplotype analysis showed that the -3223 T/Ile50 haplotype was preferentially transmitted to both AD (p < 0.01) and JCP children (p < 0.01), while that the C-3223/Ile50 haplotype was preferentially transmitted to only JCP children (p < 0.01). The association study showed that -3223 T and haplotype of -3223 T/Ile50 were associated with aD children, but not with JCP. Ile50 was associated with both AD and JCP.ConclusionsOur data suggest that -3223 T and the -3223 T/Ile50 haplotype were risk factors for AD. Ile50 allele seems to be involved in both JCP and AD. Interactions of the IL-4RA loci may play a role both conferring susceptibility and modulating severity of AD.     

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

BackgroundImatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs.AimTo investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML.MethodsOne hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C > T (rs1128503), c.3435C > T (rs1045642) and c.2677G > T/A (rs2032582) were evaluated by PCR-RFLP.ResultsABCB1 polymorphisms were not related with a risk for CML in this sample population (p < 0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p > 0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43–97.3, p = 0.022).ConclusionsThe ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients.     

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

Background and aimsA recent study reported that a nonsynonymous SNP rs2241880 (c.898A > G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A > G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.MethodsIn total, we included 910 European IBD patients and compared the ATG16L1 c.898A > G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n = 310; ulcerative colitis [UC] n = 179), Hungary (CD n = 147; UC n = 117), and the Netherlands (CD n = 157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.ResultsWe found a highly significant association of c.898A > G to CD. The association was significant (p = 0.0005) for the total CD cohort but also for the individual populations from Germany (p = 0.02) and Netherlands (p = 0.02) whereas in the Hungarian CD patients a clear trend was observed (p = 0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A > G and UC. No statistical interactions were observed between ATG16L1 c.898A > G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.ConclusionsWe confirm that ATG16L1 variant c898A > G confers a risk variant for CD but is not associated with a distinct CD phenotype.     

Circulating angiogenic cytokines and stem cells in patients with severe chronic ischemic heart disease — Indicators of myocardial ischemic burden?

BackgroundAngiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease.MethodsFifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects.ResultsPlasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34−/CD45− cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p < 0.005 − 0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p = 0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea.ConclusionsPlasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.     

Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease

ObjectiveFree fatty acid inhibition with trimetazidine (TMZ) improves myocardial metabolism and myocardial ischemia in patients with coronary artery disease (CAD). Because of its effect on myocardial glucose utilization TMZ may represent a therapeutic option in diabetic patients with CAD. Aim of the present study was to evaluate whether the metabolic effect of TMZ may improve episodes of myocardial ischemia in diabetic patients with CAD.Research design and methodsWe assessed the effect of TMZ on 24 h ambulatory ECG monitoring (AEM) in 30 patients (22 males and 8 females, mean (SE) age 67 ± 6.5 years) with NIDDM and ischemic cardiomyopathy. Patients were randomized to receive on top of standard therapy either TMZ (20 mg, tds) or placebo (tds) and were evaluated at baseline and after 6 months.ResultsPatients randomized to TMZ or placebo were comparable regarding demographic data, distribution of CAD, and glicated haemoglobin levels. TMZ significantly reduced the number of episodes of transient myocardial ischemia (− 24% compared to baseline, p < 0.01; − 27% compared to placebo, p < 0.01), and Total Ischemic Burden (− 28% compared to baseline, p < 0.01; − 29% compared to placebo, p < 0.01). TMZ also significantly reduced the number of silent episodes of myocardial ischemia (− 42% compared to baseline and − 39% compared to placebo, p < 0.01) and the time of silent myocardial ischemia/24 h (− 37% compared to baseline and − 35% compared to placebo, p < 0.01). No significant changes in heart rate were detected between baseline, placebo and TMZ evaluations.ConclusionsTMZ is effective in reducing silent and symptomatic episodes of transient myocardial ischemia in diabetic patients with CAD on standard anti-anginal therapy.     

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

Background

Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated.

Lower fasting blood glucose, glucose variability and nocturnal hypoglycaemia with glargine vs NPH basal insulin in subjects with Type 1 diabetes

Background and aimsTo compare switching from NPH insulin (NPH) to insulin glargine (glargine) with continuing NPH for changes in fasting blood glucose (FBG) in patients with Type 1 diabetes on basal–bolus therapy with insulin lispro as bolus insulin. Secondary objectives included self-monitoring blood glucose, mean daily blood glucose (MDBG) and mean amplitude glucose excursion (MAGE) values alongside changes in HbA_1c and safety profiles.Methods and resultsThis was a 30-week, parallel, open-label, multicentre study. Seven-point profiles were used to calculate MDBG and MAGE. Hypoglycaemia and adverse events were recorded by participants. FBG improved significantly with both glargine (baseline–endpoint change: −28.0 mg/dL; 95% CI: −37.3, −18.7 mg/dL; p < 0.001) and NPH (−9.8 mg/dL; 95% CI: −19.1, −0.5 mg/dL; p = 0.0374). The improvement was significantly greater with glargine than NPH (mean difference: −18.2 mg/dL; 95% CI: −31.3, −5.2 mg/dL; p = 0.0064). MDBG (−10.1 mg/dL; 95% CI: −18.1, −2.1 mg/dL; p = 0.0126) and MAGE (−20.0 mg/dL; 95% CI: −34.5, −5.9 mg/dL; p = 0.0056) decreased significantly with glargine, but not NPH although endpoint values were no different with the two insulins. Baseline to endpoint change in HbA_1c was similar (−0.56 vs −0.56%) with no differences at endpoint. Overall hypoglycaemia was no different, but glargine reduced nocturnal hypoglycaemia (“serious episodes” with BG < 42 mg/dl, p = 0.006) whereas NPH did not (p = 0.123), although endpoint values were no different.ConclusionSwitching from NPH to glargine is well tolerated and results into lower FBG, and lower glucose variability while reducing nocturnal hypoglycaemia. These data provide a rationale for more aggressive titration to target with glargine in Type 1 diabetes.     

HLA-DQ2 and -DQ8 genotypes in celiac and healthy Libyan children

BackgroundFew data are available on the prevalence of celiac disease (CD)-predisposing, HLA-related genes in Arab populations.Aim of the studyTo investigate the distribution of HLA-DQ2 and -DQ8 genotypes in Libyan children with CD and healthy controls.PatientsWe tested 31 Libyan children with CD (22 females and 9 males, median age 9.2 years) and 156 Libyan controls (81 females and 75 males, median age 10.9).MethodsHLA genes were determined on a drop of dried blood by the DQ-CD Typing Plus kit (DiaGene, Palermo, Italy).ResultsThe HLA-DQ pattern of the 31 CD children was: hetero DQ2 (n = 15), DQ2 with homo β2 (10), DQ8 and β2 positive (3), DQ8 (2), and hetero β2 (1). The HLA-DQ pattern of the 156 controls was: hetero DQ2 (n = 36), hetero β2 (30), DQ2–DQ8 negative (23), DQ8 (19), α5 (14), DQ2 with homo β (12), homo β2 (10), DQ8 and β2 positive (7), and DQ2/DQ8 (5).ConclusionsHLA-DQ2 and -DQ8 in CD patients are as common in Libya as in Italy, but the frequency of “high-risk” genotypes is higher in Libyan than Italian patients. The prevalence of HLA-DQ2 and -DQ8 genes in the Libyan general population is higher than in Italy, indicating a strong genetic predisposition to CD.     

Akt2 Gene common allelic variants in insulin resistance and the metabolic syndrome

Background and aimSeveral lines of evidence indicate that glucose homeostasis may be under the control of Akt2 and it can therefore be seen as a candidate gene for human insulin resistance (IR) and related phenotypes. The aim of our study was the identification of Akt2 common allelic variants that might modulate susceptibility to IR and related metabolic abnormalities.Methods and resultsThe Akt2 gene (exons, 5′ and 3′ regulatory regions) was re-sequenced in samples of 50 blood donors from the Gargano region. Two single nucleotide polymorphisms (SNPs) in 5′ (rs11669332 and rs969531) and two in 3′ (rs2304186 and C1658T) regulatory regions were exploited in an association study using 661 healthy unrelated Caucasian individuals from the same region.Individuals being homozygous for the T allele of rs11669332 (an Akt2 promoter) showed lower systolic blood pressure (p = 0.04), total/HDL cholesterol ratio (p = 0.02) and the metabolic syndrome score (p = 0.04), while carriers of the A allele of rs969531 (in 5′-UTR) showed higher systolic blood pressure (p = 0.027). The association between phenotypic traits and possible haplotypes was tested as well. However, no haplotype affecting the risk of metabolic abnormalities was found.ConclusionsTwo variants in 5′ regulatory region of Akt2 gene are associated and may modulate susceptibility to IR and related metabolic abnormalities.     

Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction

BackgroundMajor histocompatibility complex (MHC) gene region harbours haplotypes that associate with coronary artery disease (CAD). Their role in ST-elevation infarction (STEMI) or on the inflammatory level is not known.MethodsFour candidate MHC markers were analyzed by real-time quantitative PCR and constructed into haplotypes from patients with STEMI (n = 162), matched controls with no CAD (n = 319) and general population sample (n = 149). High sensitivity C-reactive protein (hsCRP) was assessed in a follow-up visit from patients (n = 86) and at inclusion from other study subjects.ResultsThe haplotype with one copy of HLA-DRB1*01, C4A, C4B but no HLA-B*35 doubled the risk of STEMI (OR = 2.15, 95%CI = 1.11–4.15, p = 0.020 for patients vs. controls, and OR = 2.26, 95%CI = 0.97–5.24, p = 0.052 for patients vs. population sample). The association between patients and controls persisted in multivariate analyses. The frequency of the haplotype was 5.86% (n = 19/324) in patients, 2.82% (n = 18/638) in controls and 2.68% (n = 8/298) in population sample. None of the individual MHC markers alone showed significant association with STEMI.In multivariate analyses, the haplotype carriers had higher hsCRP levels in patients (median 3.37 mg/L in carriers vs. 1.14 mg/L in non-carriers, p = 0.019) and in controls (median 2.90 mg/L vs. 1.21 mg/L, p = 0.009, respectively).ConclusionThe MHC haplotype associates with STEMI and elevated baseline hsCRP levels. The results are in concordance with previous data on non-STEMI patients, implying that a HLA-DRB1*01 – related haplotype increases the risk of CAD, possibly though increased inflammation.     

The effect of WNT5B IVS3C>G on the susceptibility to type 2 diabetes in UK Caucasian subjects

Background and aimsThe wnt signaling pathway regulates adipogenesis and insulin secretion. The WNT5B gene has been reported to confer susceptibility to type 2 diabetes (T2D) in the Japanese population, and we therefore evaluated this in Caucasian subjects with respect to obesity status.Methods and resultsTwo thousand seven hundred and one Caucasian middle-aged men from the prospective Northwick Park Heart Study II (NPHSII) of whom 153 developed T2D over 15 years and 1268 Caucasian middle-aged patients with T2D (60% male) were genotyped using a TaqMan assay for the IVS3C > G variant (rs2270031) in the WNT5B gene. The frequency of the G allele was 0.026 (0.022–0.031) in controls and 0.031 (0.025–0.039) in patients with diabetes, p = 0.24. In the prospective analysis, G allele carriers with BMI below 26 kg/m² had significantly higher T2D hazard risk [3.46 (1.34–8.96), p = 0.01]. Comparing T2D cases with NPHSII controls, the G allele was associated with a significantly higher T2D odds ratio (OR) of 1.50 (1.06–2.12), p = 0.02 in subjects with BMI lower than 30 kg/m². Increasing BMI had a smaller effect on risk in G allele carriers. The effect on risk was not explained by genotype being associated with any classical T2D risk factor. When the combined effect of this SNP and the TCF7L2 IVS3C > T SNP (rs7903146) was evaluated, a 2.07 (1.40–3.07), p < 0.0001 fold higher OR was observed in carriers of both the rare alleles.ConclusionVariation in WNT5B predisposes to T2D in the absence of obesity. The increase in risk conferred by the presence of both WNT5B and TCF7L2 variants strengthens the role of wnt signaling in T2D.     

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

PurposeIn this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.MethodsGenomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.ResultsA statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p < 0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015–2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p < 0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024–2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p > 0.05).ConclusionsThis is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.     

Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction

ObjectiveTo investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis.MethodsWe enrolled 65 patients with acute myocardial infarction (AMI, n = 22), unstable angina pectoris (UAP, n = 16), and stable angina pectoris (SAP, n = 27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14⁺CD16^? and CD14⁺CD16⁺) was measured by flow cytometry.ResultsIn patients with AMI, TLR4 was more expressed on circulating CD14⁺CD16⁺ monocytes than on CD14⁺CD16^? monocytes (p < 0.001). The expression levels of TLR4 on CD14⁺CD16⁺ monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14⁺CD16⁺ monocytes were significantly elevated at the culprit site compared with the systemic level (p = 0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p < 0.001). In addition, plasma levels of tumor necrosis factor-α were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r = 0.47, p = 0.027).ConclusionTLR overexpression on CD14⁺CD16⁺ monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI.     

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

Placenta growth factor expression in human atherosclerotic carotid plaques is related to plaque destabilization

Background and purposePlacenta growth factor (PlGF) mediates angiogenesis and inflammation, but its role in human atherosclerosis is unknown. This study was designed to test the hypothesis that PlGF-expression in human atherosclerotic carotid plaques is related to inflammation, vascularization and clinical plaque instability.MethodsThe expression of PlGF, C-reactive protein (CRP) and CD40L was analyzed with Western blots in carotid plaques of 60 patients. Cellular infiltration (CD68, CD3) and vascularization (von-Willebrand-factor) was assessed by immunohistochemistry.ResultsSymptomatic patients showed higher levels of PlGF than asymptomatic patients (115.4 ± 8.2 versus 83.6 ± 10.5 densitometric units (DU), p < 0.05) and higher grading for inflammatory cells and microvessels (CD3: 2.3 ± 0.1 versus 0.6 ± 0.1, p < 0.001, CD68: 2.4 ± 0.1 versus 0.8 ± 0.1, p < 0.001, microvessels: 2.3 ± 0.1 versus 1.5 ± 0.1, p < 0.01). PlGF-expression showed a positive correlation to the expression of CRP (r = 0.5, p < 0.001) and CD40L (r = 0.4, p < 0.01).ConclusionsPlGF-expression within human atherosclerotic lesions is associated with plaque inflammation and microvascular density, suggesting a role for PlGF in plaque destabilization and, thus, in clinical manifestation of the disease.     

Metabolic syndrome, abdominal obesity, and cardiovascular risk in elderly women

BackgroundMetabolic syndrome and abdominal obesity are risk factors for cardiovascular diseases in middle age women but, not completely understood in older people. In this study we analyzed the association between metabolic syndrome and abdominal obesity and the occurrence of cardiovascular events in these elderly women.MethodsA prospective follow-up study included 516 consecutive women aged 60–84 years who sought medical care at a geriatric outpatient facility. The presence of metabolic syndrome and higher quartiles of waist circumference and waist-to-hip ratio were analyzed as predictive variables, and were adjusted for age, smoking, and previous cardiovascular diseases. The outcomes were the occurrence of stroke, myocardial infarction, evidence of coronary artery disease, or cardiovascular death.ResultsDuring a mean follow-up of 6.6 years, 94 (18.2%) cardiovascular events were observed (48 fatal and 46 non-fatal). Metabolic syndrome was diagnosed in 206 women (39.9%). After adjustments for confounding variables, metabolic syndrome and waist-to-hip ratio above the 75th percentile (> 0.98) were predictors of the outcomes, but greater waist circumference (> 96 cm) was not. Adjusted hazard ratios for these variables were: metabolic syndrome, 1.66, 95% CI − 1.11 to 2.47, p = 0.01; waist-to-hip ratio, 1.72, 95% CI − 1.05 to 2.82; p = 0.03 and waist circumference, 1.37, 95% CI − 0.91 to 2.07, p = 0.12.ConclusionMetabolic syndrome and high waist-to-hip ratio were associated with increased risk of cardiovascular events in the studied sample.     

FADS gene polymorphisms in Koreans: association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

ObjectiveWe investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans.MethodsIn this case–control study, CAD patients (n = 756, 40–79 years) and healthy controls (n = 890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide.ResultsAmong four SNPs, only rs174537G > T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P = 0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61–0.92), P = 0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F_2α in both control and CAD groups.ConclusionThe rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.     

Fish oil,insulin sensitivity,insulin secretion and glucose tolerance in healthy people: Is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

AimTo evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, β-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid.Methods and resultsOne hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (K_G-value) were evaluated by the intravenous glucose tolerance test (IVGTT).Fish oil did not have any effect on SI, FPIR, K_G-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Δ SI 0.42 ± 0.34 on fish oil vs 0.14 ± 0.23 on placebo for those with n-6/n-3 <4.85; −1.03 ± 0.47 on fish oil vs −0.27 ± 0.32 on placebo for those with n-6/n-3 >4.85) (M ± SE), FPIR (Δ FPIR 135.9 ± 78.9 vs 157.2 ± 157.5 pmol/L; 38.8 ± 181.7 vs 357.1 ± 181.7 pmol/L), K_G-value (Δ K_G 0.14 ± 0.15 vs 0.12 ± 0.11; −0.32 ± 0.16 vs 0.15 ± 0.15) or disposition index (Δ disposition index 1465.4 ± 830.4 vs 953.8 ± 690.0; −1641.6 ± 1034.3 vs 446.6 ± 905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of K_G-value (p = 0.02).ConclusionsIn healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, β-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.