Temporal Changes in a Novel Metric of Physical Activity Tracking (Personal Activity Intelligence) and Mortality: The HUNT Study,Norway

BackgroundPersonal Activity Intelligence (PAI) is a novel activity metric that translates heart rate variations during exercise into a weekly score. Weekly PAI scores assessed at a single point in time were found to associate with lower risk of premature cardiovascular disease (CVD) mortality in the general healthy population. However, to date, the associations between long-term longitudinal changes in weekly PAI scores and mortality have not been explored.PurposeThe aim of the present study was to prospectively examine the association between change in weekly PAI scores estimated 10 years apart, and risk of mortality from CVD and all-causes.MethodsWe performed a prospective cohort study of 11,870 men and 13,010 women without known CVD in Norway. By using data from the Nord-Trøndelag Health Study (HUNT), PAI was estimated twice, ten years apart (HUNT1 1984-86 and HUNT2 1995-97). Mortality was followed-up until December 31, 2015. Adjusted hazard ratios (AHR) and 95% confidence intervals (CI) for death from CVD and all-causes related to temporal changes in PAI were estimated using Cox regression analyses.ResultsDuring a mean (SD) of 18 (4) years of follow-up, there were 4782 deaths, including 1560 deaths caused by CVD. Multi-adjusted analyses demonstrated that participants achieving a score of ≥100 PAI at both time points had 32% lower risk of CVD mortality (AHR 0.68; CI: 0.54–0.86) for CVD mortality and 20% lower risk of all-cause mortality (AHR 0.80; CI: 71–0.91) compared with participants obtaining <100 weekly PAI at both measurements. For participants having <100 PAI in HUNT1 but ≥100 PAI in HUNT2, the AHRs were 0.87 (CI: 0.74–1.03) for CVD mortality, and 0.86 (CI: 0.79–0.95) for all-cause mortality. We also found an inverse linear relationship between change in PAI and risk of CVD mortality among participants with 0 PAI (P < 0.01), and ≤50 PAI (P = 0.04) in HUNT1, indicating that an increase in PAI over time is associated with lower risk of mortality. Excluding the first three years of follow-up did not substantially alter the findings. Increasing PAI score from <100 PAI in HUNT1 to ≥100 PAI in HUNT2 was associated with 6.6 years gained lifespan.ConclusionAmong men and women without known CVD, an increase in PAI score and sustained high PAI score over a 10-year period was associated with lower risk of mortality.     

Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+ Study

Frailty is a major health problem in older people and, as the population ages, identification of its underlying biological mechanisms will be increasingly important. DNA methylation patterns within genomic DNA change during ageing and alterations in DNA methylation, particularly at gene promoter regions, can lead to altered gene expression. However the importance of altered DNA methylation in frailty is largely unknown. Using cross-sectional data from the Newcastle 85+ Study (all participants aged 85 years) frailty was operationalized by the Fried model. DNA methylation levels were assessed by highly quantitative pyrosequencing at the gene promoter associated CpG islands from a panel of five age-related methylation marker loci and at LINE-1 repetitive elements (as a surrogate for genome-wide methylation). While genome-wide methylation (as assessed at LINE-1 elements) showed no association with frailty status, there was a clear association between CpG island methylation and frailty. When compared to participants with CpG island methylation levels in the combined middle two (referent) quartiles, those in the lowest quartile had significantly decreased odds of frailty [odds ratio 0.47 (95 % CI 0.26–0.85); n = 321, p = 0.013]. Overall this study suggests a potential role for age-related changes in CpG island methylation in the development of frailty.     

Association of NT-ProBNP,Blood Pressure,and Cardiovascular Events: The ARIC Study

BackgroundAlthough intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.ObjectivesThis study examined whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.MethodsParticipants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.ResultsThere were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.ConclusionsElevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.     

Oxidized high-density lipoprotein as a risk factor for cardiovascular events in prevalent hemodialysis patients

Background and objectivesHere, we assessed the impact of oxidized high-density lipoprotein (oxHDL), dysfunctional HDL, on mortality and cardiovascular disease (CVD) events in prevalent HD patients and compared oxHDL to interleukin-6 (IL-6), a strong predictor of CVD events in HD patients.Design, setting, participants, and measurementsThis prospective study examined a cohort of prevalent HD patients (n = 412). Blood samples were obtained at baseline to measure lipids, high-sensitive C-reactive protein (hsCRP), IL-6, oxidized low-density lipoprotein, N-terminal pro B-type natriuretic peptide, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase, adiponectin, and oxHDL. Carotid intima-media thickness (CIMT) was assessed at baseline and 3-year follow-up. Nutritional status was assessed by subjective global assessment (SGA), body mass index, and geriatric nutritional risk index (GNRI). After the baseline assessment, study patients were prospectively followed up (mean observational period, 40 months).ResultsAt baseline, patients with high oxHDL had a worse nutritional state and higher HDL-cholesterol (HDL-chol), ICAM-1, and adiponectin levels and a higher oxHDL/HDL-chol ratio than low oxHDL patients. A combination of high oxHDL and high IL-6 was significantly associated with increased CIMT at baseline and a larger increase in CIMT at 3-year follow-up. High oxHDL did not predict all-cause mortality; however, it was significantly associated with CVD-related mortality and composite CVD events, particularly with concomitant high IL-6. These associations were confirmed in multivariate Cox hazard models adjusted with confounding variables.ConclusionsHigh oxHDL, particularly with concomitant high IL-6, may be associated with an increased risk of CVD events and CVD-related mortality in prevalent HD patients.     

α-Adducin gene promoter DNA methylation and the risk of essential hypertension

This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = ?0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.     

Relationship between SIRT1 gene and adolescent depressive disorder with nonsuicidal self-injury behavior: Based on gene methylation and mRNA expression

Objective:The incidence of non-suicidal self-injury (NSSI) behavior in adolescents is increasing year by year. Patients with a history of both depression and NSSI behavior tend to be at greater risk for suicide. At present, the mechanism of adolescent depressive disorder with NSSI behavior is not clear and still in research and exploration. The expression of the Silent Information Regulator 2 Related Enzyme 1 (SIRT1) gene is closely related to the level of serotonin in molecular mechanisms, and may be closely related to the occurrence and development of depressive disorder. This study aimed to explore the relationship between the SIRT1 gene and NSSI behaviors in adolescents with depressive disorder.Methods:A total of 15 adolescent depressed patients with NSSI behavior and 15 healthy controls were enrolled in the study. Bisulfite Sequencing PCR (BSP) was used to test the methylation level of SIRT1 gene promoter region of the participants. The real-time fluorescent quantitative PCR was conducted to measure the mRNA expression level of SIRT1 gene.Results:Our study found that the methylation level of SIRT1 gene promoter region at cytosine-guanine dinucleotide 5 (CpG5) site in depression group was higher than that of control group. Compared with that of control group, the plasma concentration of Sirt1 protein significantly decreased in depression group.Conclusion:Our study investigated the methylation level and the mRNA expression of SIRT1 gene in adolescent depressive patients with NSSI behavior. The study points towards finding an in vivo molecular marker for those adolescent patients.     

DNA methylation associated with healthy aging of elderly twins

Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. One approach to this goal is to find genomic sites or regions where DNA methylation correlates with biological age. Using health data from 134 elderly twins, we calculated a frailty index as a quantitative indicator of biological age, and by applying the Infinium HumanMethylation450K BeadChip technology to their leukocyte DNA samples, we obtained quantitative DNA methylation data on genome-wide CpG sites. We analyzed the health and epigenome data by taking two independent associative approaches: the parametric regression-based approach and a non-parametric machine learning approach followed by GO ontology analysis. Our results indicate that DNA methylation at CpG sites in the promoter region of PCDHGA3 is associated with biological age. PCDHGA3 belongs to clustered protocadherin genes, which are all located in a single locus on chromosome 5 in human. Previous studies of the clustered protocadherin genes showed that (1) DNA methylation is associated with age or age-related phenotypes; (2) DNA methylation can modulate gene expression; (3) dysregulated gene expression is associated with various pathologies; and (4) DNA methylation patterns at this locus are associated with adverse lifetime experiences. All these observations suggest that DNA methylation at the clustered protocadherin genes, including PCDHGA3, is a key mediator of healthy aging.     

Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation

BackgroundOncogenic insulin-like growth factor-II (IGF-II) is overexpressed in hepatocellular carcinoma (HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression.MethodsIGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration (nmol/mg protein). Status of human IGF-II promoter 3 (P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction (MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay.ResultsThe levels of hepatic IGF-II expression were significantly elevated in the HCC group (P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none (0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA (all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level (r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II (r_s = ?0.89, P < 0.001) or liver IGF-II level (r_s = ?0.84, P < 0.001).ConclusionsThe increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.     

Modification of the all-cause and cardiovascular disease related mortality risk with changes in the metabolic syndrome status: a population-based prospective cohort study in Taiwan

AimTo examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality.MethodsThis prospective cohort study consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality.ResultsOver the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio [aHR], 0.87; 95%CI, 0.82–0.92) and CVD mortality (aHR, 0.81; 95% confidence interval [CI], 0.71–0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05–1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07–1.39), compared to the MetS-free group.ConclusionRecovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk.     

Regular use of ibuprofen or paracetamol and incident type 2 diabetes: A prospective cohort study in the UK Biobank

BackgroundThe relation of regular ibuprofen or paracetamol use with the risk of type 2 diabetes (T2DM) remained undetermined. We aimed to evaluate the prospective association between regular ibuprofen or paracetamol use and incidence of T2DM.MethodsThis cohort included 372,843 participants with available data of ibuprofen, paracetamol use and without diabetes at baseline from the UK Biobank. The primary outcome was incident T2DM. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of T2DM.ResultsDuring a median of 12.1 years’ follow-up, 11,527 (3.1%) participants developed T2DM. Overall, participants with regular use of paracetamol showed a significantly higher risk of incident T2DM (adjusted HR, 1.25; 95%CI: 1.19,1.31), compared with non-users. Moreover, a stronger positive association of paracetamol use with incident T2DM was found among those aged <60 years (vs. ≥60 years, P-interaction =0.008), free of cardiovascular diseases (CVD) (vs. CVD patients, P-interaction =0.01), and without the use of anti-hypertensive drugs (vs. users, P-interaction =0.016) at baseline. However, there was no significant association between regular use of ibuprofen (users vs. non-users; adjusted HR, 1.05; 95%CI: 0.99,1.12) and incident T2DM. More importantly, genetic risks of T2DM did not significantly modify the relations of ibuprofen, or paracetamol use with incident T2DM (Both P-interactions >0.05).ConclusionsRegular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of incident T2DM among middle aged UK adults. Our current findings highlight the need for greater consideration in the clinical selection of paracetamol or ibuprofen.     

B-vitamins intake,DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: The EPICOR study

Background and aimsSeveral epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake.Methods and resultsStudy sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5′UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5′UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 × 10⁻⁴ and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed.ConclusionsOur findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake.     

Examination of ATM,BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer

BackgroundPancreatic cancer is a lethal disease with a poor 5-year survival rate. Pathogenic germline variants in the coding regions of ATM, BRCA1, and BRCA2 are found in up to 4.8% of pancreatic cancer patients. Germline promoter methylation and gene silencing arising from a germline variant or through other mechanisms have been described as a cause of tumor suppressor gene inactivation.MethodsWe measured the level of promoter methylation of the ATM, BRCA1, and BRCA2 genes in peripheral blood lymphocytes from 655 patients with pancreatic cancer using real-time PCR.ResultsNo evidence of germline promoter methylation of any of these genes was found. Promoter methylation levels were minimal with no patient having promoter methylation greater than 3.4%, 3.3%, and 7.6% for ATM, BRCA1 and BRCA2, respectively, well below levels found in patients who have inherited promoter methylation (∼50%).ConclusionsWe found no evidence of germline promoter methylation for the pancreatic susceptibility genes ATM, BRCA1 and BRCA2 in patients with pancreatic cancer. This study reveals that constitutive germline methylation of promoter CpG islands is rare in pancreatic cancer.     

Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4

Background: Maternal cannabis use in pregnancy is linked with long-term adverse behavioral outcomes in offspring. Epigenetic processes established in utero that affect dopaminergic (reward) signaling may mediate risks. Associations between cannabis use and offspring DNA methylation have not been investigated; however, maternal tobacco smoking in pregnancy is associated with distinct patterns of DNA methylation at birth and beyond. Objectives: To determine whether maternal cannabis use is associated with methylation of the dopamine receptor gene DRD4 promoter in infants. Methods: Mothers in the Triple B study provided detailed information on drug use in each trimester of pregnancy. Buccal swabs were collected from neonates at 8 weeks (n = 804, 51.7% male, and 48.3% female). DRD4 promoter DNA methylation was measured using SEQUENOM MassARRAY. Results: Fifty-seven of the women in the study reported drug use during pregnancy, of whom 44 used cannabis. Of 19 cytosine-phosphate-guanine dinucleotides (CpG) units tested in DRD4, gestational cannabis use was associated with offspring methylation at 1 CpG unit in multivariate models (β + 1.48, CI: 0.02 to 2.93, and p = 0.047). At another site there was weak evidence that both cannabis and other drug use were independently associated with increased methylation, while the association with tobacco was in the reverse direction (cannabis use β + 0.67, CI: ?0.12 to 1.46, and p = 0.09; other drug use β + 1.11, CI: 0.17 to 2.05, and p = 0.02; tobacco use β ?0.41, CI: ?0.85 to 0.03, and p = 0.07). None of the associations would remain significant after correction for multiple testing. Conclusion: There is no strong evidence that maternal cannabis use in pregnancy is associated with offspring DRD4 methylation.     

The association of dietary macronutrients composition with the incidence of cardiovascular disease,using iso-energetic substitution models: Tehran lipid and glucose study

Background and aimsDietary macronutrient composition plays an important role in the prevention of cardiovascular disease (CVD). This study aimed at assessing the iso-energetic substitution of dietary macronutrients in relation to the incidence of CVD.Materials and resultsThis prospective study was conducted on 5102 individuals of Tehran lipid and glucose study participants, aged 20–70 years who were followed for 5.3 years. A valid and reliable semi-quantitative food frequency questionnaire was used to assess dietary intakes. The hazard ratio of CVD for each 5% of energy from macronutrients at the expense of another macronutrient was calculated using the substitution model.During follow-up, a total of 206 CVD outcomes were identified. Mean age of participants (44.2% men) was 47.0 ± 12 and 45.6 ± 11 for men and women, respectively. Substituting 5% of energy from all types of macronutrients by 5% percentage of energy from combined saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) was associated with a decrease in the risk of CVD by almost 20%. Higher energy intake from total-, starchy-, and nonstarchy carbohydrates replaced by other macronutrients was not significantly associated with the risk of CVD. Each 5% of energy from animal protein (HR: 1.09 and CI: 1.02–1.16) independently increased the risk of CVD in the adjusted Cox proportional hazard regression analyses.ConclusionHigher percentage of energy from animal protein independently increased the risk of CVD, replacement of SFA and MUFA together with other macronutrients was inversely associated with CVD risk.     

Janus kinase 2 (JAK2) methylation and obesity: A Mendelian randomization study

Background and aimsJanus kinase 2 (JAK2) play an important role in the energy metabolism. Whether there is a causal relationship between JAK2 methylation levels and obesity remains unclear. Based on the instrumental variables of 5 SNP sites, this study was aimed to explore the causal relationship between JAK2 methylation levels and obesity by Mendelian randomization analysis.Methods and resultsA total of 1021 participants (511 cases and 510 controls defined by body mass index (BMI) ≥ 28.0 kg/m²) was conducted from the Henan Rural Cohort study. SNPscan® was performed to test the SNP genotyping and MethylTarget™ was applied to detect the DNA methylation level. The logistic regression model was used to evaluate the associations between SNP or methylation of JAK2 and obesity (according to BMI). Mendelian randomization analysis was used to assess the potential causal association between JAK2 methylation and obesity. According to the logistic regression model, 1 CpG sit in the promotor was related to an increased risk of obesity (P < 0.05). 10 CpG sites in the exon were associated with decreased risk of obesity (P < 0.05). Mendelian randomization analysis showed a causal association between the methylated level of JAK2 and obesity, based on the instrumental variables of 5 SNPs (P < 0.05).ConclusionsThis study supported that the methylation degree of JAK2 has a complex relationship with obesity, which might be related to the region of methylation. A causal relationship exists between the methylated level of JAK2 and obesity.     

Genome-wide DNA methylation profiling in nonalcoholic fatty liver reveals predictive aberrant methylation in PRKCE and SEC14L3 promoters

BackgroundOptimal non-invasive biomarkers for diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) remain to be identified.AimsTo identify potential DNA methylation biomarkers for NAFLD.MethodsGenome-wide DNA methylation profiling was performed to identify differentially methylated CpG sites in peripheral blood leukocytes. Differentially methylated regions were validated using the MassCLEAVE assay. The expression levels of candidate genes were explored by Gene Expression Omnibus database.ResultsThe hypomethylation of PRKCE CpG 4.5 and CpG 18.19 was associated with nonalcoholic fatty liver (NAFL), the odds ratio (OR) and 95% confidence interval (CI) were 0.129 (0.026–0.639) and 0.231 (0.069–0.768). The methylation level of CpG 1.2 and average methylation level of SEC14L3 were correlated with NAFL, with OR (95% CI) being 0.283 (0.093–0.865) and 0.264 (0.087–0.799). PRKCE CpG 4.5 and cg17802464 of SEC14L3 were correlated with body mass index, waist circumference, total triglyceride, high-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase. All selected datasets showed high expression levels of PRKCE and SEC14L3 in patients with NAFLD.ConclusionsOur findings suggest that the hypomethylation of PRKCE and SEC14L3 promoters represent attractive biomarkers for NAFLD. Further studies are warranted to validate these biomarkers as molecular tools for diagnosis of NAFLD and therapeutic targets.     

Incremental risk of cardiovascular disease and/or chronic kidney disease for future ASCVD and mortality in patients with type 2 diabetes mellitus: ACCORD trial

BackgroundCardiovascular disease (CVD) and chronic kidney disease (CKD) are complications of type 2 diabetes mellitus (DM). Current cholesterol guidelines recommend the same prevention strategy for patients with DM alone as patients with DM + CKD. However, the incremental risk of these common complications for incident cardiovascular disease and mortality has not been well studied.MethodsWe compared the incremental risk of having DM + CKD, DM + CVD and DM + CVD + CKD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants for incident CVD as the primary outcome and all-cause mortality.ResultsAfter a mean (SD) follow up of 4.7(1.4) years, 1,046(10%) participants developed CVD. DM +vCKD, DM + CVD, and DM + CKD + CVD had a significantly increased risk of the primary outcome compared to DM alone [adjusted hazard ratio(95%CI): 1.41 (1.06-1.89), p = 0.02; 2.20 (1.92-2.53), p < 0.001); 2.35 (1.81-3.04), p < 0.001), respectively]. All-cause mortality had a graded increased risk compared to the reference group [adjusted hazard ratio(95%CI): 1.39 (1.01-1.90), p = 0.04; 1.29 (1.51-2.12), p < 0.0001; 2.36 (1.75-3.13), p < 0.0001), respectively].ConclusionOur post hoc analysis shows an incremental graded risk for CVD outcomes and all-cause mortality with the development of CKD and/or CVD in individuals with DM.     

Low-carbohydrate diet and cardiovascular diseases in Iranian population: Tehran Lipid and Glucose Study

Background and aimsStudies indicated that the risk of cardiovascular disease (CVD) in association to greater adherence to low-carbohydrate diet (LCD) differs in various populations. In this study, we aimed to assess the association of LCD score with the risk of CVD events in a prospective population-based study.Methods and resultsCVD-free participants (n = 2188) were recruited from the Tehran Lipid and Glucose Study (2006–2008) and followed for a mean of 6.7 years. Using a valid and reliable 168 item semi-quantitative food frequency questionnaire, the LCD score was determined based on the percentage of energy as carbohydrate, protein, and fat, which ranged from 0 to 12. Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) of CVD across tertiles of LCD score in women and men.Mean ± SD age of participants (44.8% male) was 38.8 ± 13.0 years, and median (25–75, interquartile range) of the LCD score was 6 (4–8) at baseline. During follow-up, 77 (3.5%) new cases of CVD were identified. After adjustment for sex, age, body mass index, physical activity, smoking, energy intake, diabetes, and hypertension, there was no association between the LCD score and risk of CVD outcomes in all participants (HR = 0.93; 95% CI: 0.86–1.02) and women (HR = 1.13; 95% CI: 0.94–1.36); however, the LCD score was associated with an 11% reduced incidence of CVD events in men (HR = 0.89; 95% CI: 0.80–0.98), (P for trend: 0.028).ConclusionFindings showed that higher adherence to LCD may be associated with a lower risk of CVD outcomes in men but not in women.