Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macro-albuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus

ObjectivesTo find whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are risk factors for diabetic nephropathy (DN) among type 2 diabetes mellitus (T2DM) patients from Western Iran.Design and methodsThe MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric and 72 normoalbuinuric T2DM patients by PCR-RFLP.ResultsThe possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients by 4.1 and 5.5 times (p = 0.027, and p = 0.006, respectively). The concomitant presence of both 677T and 1298C alleles act in synergy to increase the risk of macroalbuminuria by 20.4-fold (p < 0.001) and progression of DN from microalbuminuria to macroalbuminuria (OR = 4.73, p = 0.01).ConclusionBoth MTHFR 677T and 1298C alleles increased the susceptibility to the onset and progression of DN in Iranians with T2DM.     

Relationship between genetic polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase as risk factors for type 2 diabetes in Tunisian patients

Background/aimsThe role of methylenetetrahydrofolate reductase (MTHFR) and angiotensin-converting enzyme (ACE) gene polymorphisms as being risk factors for diabetes is still controversial. The aim was to investigate the distribution of ACE and MTHFR genotypes as well as to evaluate the role of plasmatic total homocysteine levels (tHcy) and ACE activity in Tunisian patients with type 2 diabetes mellitus (T2DM).Design and methods115 T2DM patients compared to 116 healthy volunteers.ResultsThe ACE I/D polymorphism was significantly associated with diabetes (p < 0.0001). The DD genotype and D allele were more frequent in patients compared to control group [DD: OR = 4.93; p < 0.0001; 95 % CI: 2.71–8.97; D: OR = 3.08, 95% CI: 2.09–4.51 p < 0.0001]. MTHFR allele and genotype frequencies did not differ between patients and controls. The susceptibility to diabetes in individuals with genotypes DD +vTT was 13.39 and in the individuals with DD + CT was 6.57 times that of the controls. However, individuals with genotypes ID + CC or II + CT have a protective effect against diabetes. The DD and TT genotypes were associated with significantly higher ACE activity and tHcy levels in diabetics.ConclusionOur data suggest that ACE ID polymorphism may act synergistically with MTHFR C677T polymorphism to assess diabetes risk.     

CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

BackgroundThe genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress.MethodsIn a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, ?3860G/A of CYP1A2 and ?930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx).ResultsCOPD patients had significantly increased MDA concentration (p < 0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤ 0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and ?930G, 242C of CYBA (p < 0.001, p = 0.003, p = 0.030 and p = 0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and ?930G:242C (p = 0.048, p = 0.016 and p = 0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p = 0.001 and p = 0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and ?930AG+GG of CYBA associated with increased MDA concentration (p = 0.018, p = 0.045 and p = 0.017, respectively), decreased CAT activity (p < 0.0001, p = 0.080 and p < 0.0001, respectively) and GSH concentration (p < 0.0001, p = 0.0002 and p = 0.011, respectively) in patients.ConclusionThe identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD.     

Polymorphisms of the NOS3 gene in Southern Chilean subjects with coronary artery disease and controls

BackgroundNitric oxide (NO) from the endothelium, produced by oxidation of l-arginine to l-citruline for the action at the endothelial nitric oxide synthase (eNOS) is considered an important atheroprotective factor. The 894G>T, ? 786T>C and 4a/4b polymorphic variants of the NOS3 gene have been implicated in the development of coronary artery disease (CAD). We investigated the association between occurrence of CAD documented by angiography and the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 gene in Southern Chilean individuals.MethodsA total of 112 unrelated patients with diagnosis of CAD confirmed by angiography and 112 controls were included in this study. The 894G>T and ? 786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a/4b polymorphism just for PCR.ResultsThe genotype distribution and the relative allelic frequencies for the 3 variants investigated were not significantly different between CAD and control subjects (p = NS). Moreover, the odds ratio for CAD associated with the 894T (OR = 1.22, 95% CI 0.76–1.95), ? 786C (OR = 1.16, 95% CI 0.75–1.80) and 4a (OR = 0.97, 95% CI 0.48–1.95) variants failed to reach statistical significance.ConclusionThese findings suggest that the 894G>T, ? 786T>C and 4a/4b polymorphisms of the NOS3 were not associated with CAD in the studied subjects.     

Apolipoprotein M promoter polymorphisms alter promoter activity and confer the susceptibility to the development of type 1 diabetes

ObjectivesApolipoprotein M plays an important role in the formation of preβ-HDL and cholesterol efflux to HDL. In the present study, we investigate the potential association between the ApoM promoter polymorphisms and type 1 diabetes.Design and methodsThe study was conducted in Peking Union Medical College, Beijing, China and Karolinska Institutet, Stockholm, Sweden. Two populations, including 493 Han Chinese subjects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065A, T-855C and T-778C in the promoter region of the ApoM gene are genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Promoter activity was measured by reporter gene assay.ResultsSNP T-778C was strongly associated with T1D in both Han Chinese (p = 0.002, OR = 2.188, CI 95% = 1.338–3.581) and Swedish (p = 0.021, OR = 2.865, CI 95% = 1.128–7.278) populations. The luciferase activity of ?778C promoter was 1.41 times as high as that of ?778T promoter (9.90 ± 1.92 vs. 7.04 ± 0.76, p = 0.001).ConclusionsAllele C of SNP T-778C may increase promoter activity and confer the risk susceptibility to the development of T1D.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population

ObjectiveCoronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility.Designs and methodsWe examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS).ResultsWhen the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR = 1.36, 95% CI = 1.02–1.82, p = 0.038; GA/AA vs GG: adjusted OR = 1.33, 95% CI = 1.01–1.76, p = 0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.ConclusionsThese findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population.     

Identification of NPPA variants associated with atrial fibrillation in a Chinese GeneID population

BackgroundA frameshift mutation in the NPPA gene was identified in 1 family with atrial fibrillation (AF), however, further studies are needed to establish unequivocally the genetic association between NPPA and AF.MethodsA case control association study and mutational analysis of NPPA were performed with 384 sporadic AF patients and 844 controls from a Chinese GeneID population. Genotyping was performed using High-Resolution Melt analysis. Mutational analysis was performed using direct DNA sequencing analysis.ResultsSignificant allelic association was detected between single nucleotide polymorphism (SNP) rs5063 and lone AF (p = 0.015, OR = 1.63; adjusted p = 0.003). Genotypic association was significant assuming an additive or dominant model (adjusted p = 0.005 and 0.007, respectively). Six new variants were identified in NPPA, including 2 in the 5′-UTR, 2 in the 3′-UTR, and 2 missense substitutions. Variants c.413T > C, c.*48G > A and c.*133G > T were not present in 844 controls, and the others were identified in controls.ConclusionsVariants in NPPA confer risk of lone AF in a Chinese population. Thus, in addition to being a disease-causing gene with mutations identified in familial AF cases, NPPA is a susceptibility gene for lone AF.     

A meta-analysis of the bradykinin B2 receptor gene − 58C/T polymorphism with hypertension

Background and objectiveNumerous studies have attempted to associate ? 58C/T polymorphism of bradykinin B2 receptor gene (BDKRB2) with hypertension, whereas results were often irreproducible. We performed a meta-analysis aiming to provide a comprehensive evaluation of this polymorphism and hypertension.MethodsCase-control reports published in English were searched totaling four studies with six populations (823 cases and 916 controls). Random-effects model was applied irrespective of between-study heterogeneity, and study quality was assessed in duplicate.ResultsCompared with ? 58C allele carriers, those with ? 58T allele had a lower yet nonsignificant risk for hypertension (OR = 0.86; 95% CI: 0.68–1.09; P = 0.21). Lack of significance persisted after combining those with genotypes ? 58TC and ? 58TT together (OR = 0.87; 95% CI: 0.67–1.09; P = 0.21) or with ? 58TC and ? 58CC together (OR = 0.75; 95% CI: 0.48–1.18; P = 0.22) in association with hypertension. Sensitivity analyses by race indicated that comparison of ? 58T versus ? 58C generated a protective effect for hypertension in Asians (OR = 0.77; 95% CI: 0.58–1.02; P = 0.07) and African-Americans (OR = 0.65; 95% CI: 0.43–0.98; P = 0.04), but a risk effect in Caucasians (OR = 1.22; 95% CI: 0.92–1.61; P = 0.17). No publication bias was observed.ConclusionsOur results suggested that ? 58T allele exhibited a protective effect on hypertension in Asians and African-Americans, yet a risk effect in Caucasians.     

Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

BackgroundImpaired ubiquitin–proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD).MethodsWe conducted a case–control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD.ResultsNo significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls ≥ 60 years of age (P = 0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals ≥ 60 years of age (OR = 0.61; 95% CI = 0.41–0.90, P = 0.010). This is also true for T allele (OR = 0.64; 95% CI = 0.44–0.91, P = 0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR = 0.42; 95% CI = 0.22–0.81, P = 0.009) and UCHL1 C-carrying genotype (OR = 0.67; 95% CI = 0.47–0.97, P = 0.032).ConclusionsOur results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people ≥ 60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.     

Association of haplotypes in the IL8 gene with susceptibility to chronic periodontitis in a Brazilian population

BackgroundInterleukin 8 (IL-8) is a chemokine related to the initiation and amplification of acute and chronic inflammatory processes. Polymorphisms in the IL8 gene have been associated with inflammatory diseases. We investigated whether the ? 845(T/C) and ? 738(T/A) single nucleotide polymorphisms (SNPs) in the IL8 gene, as well as the haplotypes they form together with the previously investigated ? 353(A/T), are associated with susceptibility to chronic periodontitis.MethodsDNA was extracted from buccal epithelial cells of 400 Brazilian individuals (control n = 182, periodontitis n = 218). SNPs were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Disease associations were analyzed by the χ² test, Exact Fisher test and Clump program. Haplotypes were reconstructed using the expectation-maximization algorithm and differences in haplotype distribution between the groups were analyzed to estimate genetic susceptibility for chronic periodontitis development.ResultsWhen analyzed individually, no SNPs showed different distributions between the control and chronic periodontitis groups. Although, nonsmokers carrying the TTA/CAT (OR = 2.35, 95% CI = 1.03–5.36) and TAT/CTA (OR = 6.05, 95% CI = 1.32–27.7) haplotypes were genetically susceptible to chronic periodontitis. The TTT/TAA haplotype was associated with protection against the development of periodontitis (for nonsmokers OR = 0.22, 95% CI = 0.10–0.46).ConclusionAlthough none of the investigated SNPs in the IL8 gene was individually associated with periodontitis, some haplotypes showed significant association with susceptibility to, or protection against, chronic periodontitis in a Brazilian population.     

Association of the MS4A2 gene promoter C-109T or the 7th exon E237G polymorphisms with asthma risk: A meta-analysis

Background and objectiveA large number of studies have examined the association between the Membrane-spanning 4 domains, superfamily A, number 2 (MS4A2) gene C-109T (rs1441586) or E237G (rs569108) variants and asthma risk. However, the results are inconsistent and inconclusive. To derive a more precise estimation, a meta-analysis was performed.MethodsMeta-analyses were conducted with the data from case–control association studies (24 studies with 4496 asthmatics and 4571 controls for E237G variant and 9 studies including 2005 cases and 1868 control for C-109T polymorphisms, respectively). Random-effects model was used to calculate summary odds ratios (ORs).ResultsFor the MS4A2 gene E237G variant, no significant associations with asthma were found in overall population; we observed an elevated risk of atopic asthma among subjects with the 237G allele (OR = 1.341, 95% CI: 1.039–1.732 for G versus E and OR = 1.374, 95% CI: 1.032–1.828 for EG + GG versus EE) in the stratified meta-analysis. As for the MS4A2 gene C-109T polymorphism, no significant associations with asthma risk were observed in the total population; in subgroup analysis by ethnicity of subjects we found increased asthma risk among Asians carrying T allele (OR = 1.140, 95% CI: 1.019–1.276 for T versus C and OR = 1.359, 95% CI: 1.029–1.794 for TT versus CC).ConclusionsData indicated that the MS4A2 gene E237G variant may be a risk factor for developing atopic asthma and the promoter -109T allele is a potential risk factor of asthma in Asians.     

The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese diffuse large B cell lymphoma patients

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR = 1.48, 95% CI: 1.08–2.02, Pc = 0.03; GT: OR = 1.96, 95% CI: 1.25–3.07, Pc < 0.01), while genotype AT in this locus seemed to be protective (OR = 0.29, 95% CI: 0.02–0.72, Pc = 0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR = 2.38, 95% CI: 1.52–3.74, Pc < 0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR = 5.21, 95% CI: 2.58–10.54, Pc < 0.01); haplotype of G-T in 2677–3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR = 3.97, 95% CI: 2.31–6.85, Pc < 0.01; 2677GT/3435TT: OR = 4.55, 95% CI: 2.02–10.22, Pc < 0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677–3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.     

Characteristics associated with informed consent for genetic studies in the ACCORD trial

BackgroundPrior studies found that some groups have lower genetic consent rates than others. Participant consent for genetic studies enables randomized trials to examine effects of interventions compared to control in participants with different genotypes.MethodsUnadjusted and multivariate associations between genetic consent rates and participant, study, and consent characteristics in 9573 participants approached for genetics consent in the multicenter Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics consent.ResultsEighty-nine percent of eligible participants consented to genetic studies (“Any Consent”) and 64.7% consented to studies of any genes by any investigator (“Full Consent”), with similar rates in randomized groups. Controlling for multiple characteristics, African-Americans had lower consent rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR = 0.67, p < 0.0001). Those with high school or higher education level had higher rates than less than high school graduates (Full Consent ORs 1.41–1.69, p-values < 0.0001). Consent rates were lower when genetics consent was separate from the main trial consent on the same day (Any Consent OR 0.30; Full Consent OR 0.52, p values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full Consent OR 0.76, p = 0.0002).ConclusionHigh rates of consent for genetic studies can be obtained in complex randomized trials, with lower consent rates in African-Americans, in participants with less than high-school education, and for sharing samples with other investigators. A genetics consent separated from the main trial consent was associated with lower consent rates.     

Clinical significance of Stratifin,ERα and PR promoter methylation in tumor and serum DNA in Indian breast cancer patients

Objectives:The objective of this study was to determine the concordance of promoter methylation of stratifin, ERα and PR in tumor and circulating DNA in breast cancer patients and their association with clinicopathological parameters and disease prognosis.Design and methods:Methylation specific PCR were carried out to investigate the promoter methylation status of stratifin, ERα and PR in tumor and circulating DNA in 100 breast cancer patients in a prospective study. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry.Results:Significant association was observed between promoter methylation of stratifin in tumors (61%) and paired sera (56%) (r = 0.78; p ≤ 0.001). Loss of stratifin expression was observed in 47% tumors and was associated with poor overall survival (p = 0.05). Significant correlation was observed between methylation status of ERα with PRB (p < 0.0001, OR = 20.8, 95% CI = 7.4–58.0) and stratifin (p = 0.003, OR = 2.0, 95% CI = 0.8–4.4).Conclusion:This study underscores the potential utility of serum DNA methylation of these genes as surrogate for tumor DNA methylation as a promising tool for cancer diagnosis.     

Correlation of endothelin 1 plasma levels with plasma antioxidant capacity in elderly patients treated for hypertension

Experimental studies confirmed that reactive oxygen species increase endothelin-1 (ET-1) synthesis, and modulate ET-1 signaling pathway resulting in vasoconstriction and vascular remodeling.The aim of this study was to evaluate the relationship between plasma ET-1 concentration and antioxidant status in patients with essential hypertension and type 2 diabetes mellitus.Methods78 hypertensive patients, 53.8% diabetic, mean age 72.1 ± 7.07 were examined. The plasma concentration of glucose, creatinine, uric acid, bilirubin, cholesterol, insulin, HbA1c and ET-1 were measured. Antioxidant status was assessed by Ferric Reducing Ability of Plasma (FRAP), vitamin C concentration and erythrocyte superoxide dismutase (SOD) activity.ResultsWith diabetes ET-1 concentration was higher (1.35 ± 0.51 vs 1.12 ± 0.46 pg/mL, p = 0.04). The negative correlations between ET-1 concentration and FRAP (r = ? 0.50, p < 0.0001), vitamin C (r = ? 0.296, p = 0.01) and SOD (r = ? 0.44, p = 0.001) were found. Concentration of ET-1 correlated positively with SBP (r = 0.33, p = 0.005) but not with DBP. The relationship between DBP and ET-1 only in subjects with DBP > 110 mm Hg and FRAP < 0.40 mmol/L was found. In multiple regression analysis plasma ET-1 levels were associated independently with FRAP (beta = ? 0.583, p = 0.003) and plasma vitamin C (beta = ? 0.407, p = 0.04).ConclusionsIn hypertensive and diabetic patients higher plasma endothelin-1 level was independently associated with lower plasma antioxidant status measured by FRAP and decreased vitamin C concentration, which may be a result of increased oxidative stress in these diseases.     

Independent risk factors for postoperative pain in need of intervention early after awakening from general anaesthesia

Despite advances in postoperative pain management, the proportion of patients with moderate to severe postoperative pain is still ranging 20–80%. In this retrospective study, we investigated 1736 patients to determine the incidence of postoperative pain in need of intervention (PPINI)defined as numeric rating scale >4 at rest in the post anaesthesia care unit early after awakening from general anaesthesia, and to identify possible risk factors. The proportion of patients with PPINI was 28.5%. On multivariate analysis, younger age (OR = 1.300 [1.007–1.678], p = 0.044), female gender (OR = 1.494 [1.138–1.962], p = 0.004), obesity (OR = 1.683 [1.226–2.310], p = 0.001), use of nitrous oxide (OR = 1.621 [1.110–2.366], p = 0.012), longer duration of surgery (OR = 1.165 [1.050–1.292], p = 0.004), location of surgery (musculoskeletal OR = 2.026 [1.326–3.095], p = 0.001; intraabdominal OR = 1.869 [1.148–3.043], p = 0.012), and ASA-PS I–II (OR = 1.519 [1.131–2.039], P = 0.005) were identified as independent risk factors for PPINI. Patients with PPINI experienced significantly more PONV (10.3% vs. 6.2%, p = 0.003), more psychomotor agitation (5.5% vs. 2.7%, p = 0.004), needed more application of opioid in PACU (62.8% vs. 24.2%, p < 0.001), stayed significantly longer in PACU (89.6 min [70–120] vs. 80 min [60–100], p < 0.001), had a longer median length of hospital stay (6.6 days [4.0–8.8] vs. 6.0 days [3.2–7.8]], p < 0.001), and longer postoperative stay (5.0 days [3.0–6.5] vs. 4.1 days [2.5–5.8], p < 0.001]). Patients with PPINI required more piritramid (8.0 mg [5.0–12.0] vs. 5.0 mg [3.0–7.8], p < 0.001) in PACU than patients without. The identification of patients at high risk for immediate postoperative pain in need of intervention would enable the formation of effective postoperative pain management programs.     

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BackgroundAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.MethodsWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.ResultsWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P = 0.025, OR = 1.47, 95% CI = 1.05–2.06; P = 0.023, OR = 1.53, 95% CI = 1.06–2.22) and adults (P = 0.018, OR = 1.10, 95% CI = 1.02–1.19; P = 0.001, OR = 1.16, 95% CI = 1.06–1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P = 0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P = 0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.ConclusionsFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.     

Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence

ObjectiveTo relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence.Design and methodsPON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients with recurrence of breast cancer. Results were compared between patients surviving more than one year after the analysis (22) and those who died within one year (28).ResultsIn a logistic regression analysis, ARE was negatively associated with early death (OR = 0.10 [0.02–0.58], p = 0.0109). PON did not reach significance (OR = 0.43 [0.17–1.11], p = 0.0826). In a multiple logistic regression analysis model, ARE was independently associated with early death (OR = 0.12 [0.02–0.98], p = 0.0476), besides interval time between diagnosis and recurrence (OR = 0.54 [0.27–1.07], p = 0.0781) and undernutrition (OR = 3.95 [0.81–19.19], p = 0.0883).ConclusionParaoxonase is a potential marker of survival in patients with breast cancer recurrence.