Association between SIRT6 Methylation and Human Longevity in a Chinese Population

2020 ◽  
pp. 1-10
Author(s):  
Xu Tang ◽  
Yi Wei ◽  
Jian Wang ◽  
Shiyi Chen ◽  
Jiansheng Cai ◽  
...  

<b><i>Background:</i></b> <i>Sirtuin</i> 6 gene (SIRT6) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between SIRT6 methylation and longevity has not been clarified. <b><i>Methods:</i></b> We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of <i>SIRT6</i> promoter CpG sites. qRT-PCR and ELISA were used to estimate the <i>SIRT6</i> messenger RNA (mRNA) levels and protein content. Six CpG sites (P1–P6) were identified as methylation variable positions in the <i>SIRT6</i> promoter region. <b><i>Results:</i></b> At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of <i>SIRT6</i> decreased in the control group (<i>p</i> &#x3c; 0.0001 and <i>p</i> = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (<i>r</i><sub>s</sub> = −0.173, <i>p</i> = 0.011) and P5 sites (<i>r</i><sub>s</sub> = −0.207, <i>p</i> = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (<i>r</i><sub>s</sub> = 0.136, <i>p</i> = 0.046) but showed no significant correlation with the methylation rate at the P2 site. <b><i>Conclusion:</i></b> The low level of <i>SIRT6</i> methylation may be a potential protective factor of Chinese longevity.

PEDIATRICS ◽  
1964 ◽  
Vol 33 (1) ◽  
pp. 115-119
Author(s):  
WILMER C. WISER ◽  
FRANCES R. BEIER

Meconium samples were collected from 5 newborn infants, who had a known family history of cystic fibrosis of the pancreas but who did not present with meconium ileus, and 11 normal newborn infants. Extracts of the meconium samples were examined for the presence of serum proteins by paper and immunoelectrophoresis. Three of the infants who had a family history of cystic fibrosis of the pancreas showed protein in their meconium, and this was identified by immunoelectrophoresis as consisting mainly of albumin; each of these babies subsequently developed classic symptoms of cystic fibrosis of the pancreas. The two remaining infants had no albumin in the meconium and did not develop signs of cystic fibrosis. None of the meconium samples of the control group of infants contained detectable amounts of albumin. Possible sources of the abnormal protein content of meconium are discussed, and the suggestion that the finding of albumin in meconium of newborn infants may prove to constitute a valuable diagnostic procedure for screening newborn infants for cystic fibrosis of the pancreas is advanced.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Eva Rye Rasmussen ◽  
Christian von Buchwald ◽  
Mia Wadelius ◽  
Sumangali Chandra Prasad ◽  
Shailajah Kamaleswaran ◽  
...  

Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995–2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26–86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were “DT783 Quincke’s oedema” and “DT78.4 Allergy unspecified”. Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor.


1981 ◽  
Vol 139 (1) ◽  
pp. 38-42 ◽  
Author(s):  
R. C. B. Aitken ◽  
J. A. Lister ◽  
C. J. Main

SummaryThe psychological and physiological features of 20 aircrew consecutively referred for treatment of anxiety symptoms when flying were compared with a matched control group of uncomplaining aircrew. There were no significant differences between the two groups on psychometric tests of personality, though there were differences in skin conductance; the phobics had a higher rate of spontaneous fluctuation, and habituated less to a repeated auditory tone. More of the phobic group worried about their wives and acknowledged childhood and other adulthood phobias; more had a family history of an episode perhaps best described as flying trauma. Many were on an overseas posting when symptoms presented. These few features could correctly classify 85 per cent of the subjects into the phobic or control group. This type of ‘phobic aircrew index’ now requires to be validated prospectively for its predictive value.


2020 ◽  
Author(s):  
Michał Ambroziak ◽  
Katarzyna Niewczas-Wieprzowska ◽  
Agnieszka Maicka ◽  
Andrzej Budaj

Abstract Background. Premature coronary artery disease belongs to the most pressing global issues in a modern cardiology. Family history appears to be one of the most important and significant risk factors in young patients with myocardial infarction (MI). The aim of the study was to investigate the role of family history of premature cardiovascular disease (CVD) in patients <50 years with myocardial infarction (MI) compared to patients ≥ 50 years with MI and to young healthy people.Methods. The studied group (MI<50) consisted of 240 patients aged 26-49 years with MI. The control groups consisted of 240 patients (MI≥50) with MI aged 50-92 years and 240 healthy people aged 30-49 years.Results. There were statistically significant differences between the MI<50 and MI≥50 and young healthy groups regarding family history of premature MI/ischaemic stroke and percent of patients with of ≥2 relatives affected including parents, children, siblings, siblings of parents and grandparents (10.8%, 2.9%, 3.7%, respectively; p<0.0001). There was a statistically significant negative correlation between the age of the first episode of MI and the number of relatives with a history of premature MI/stroke (r=0.249, p<0.05) within all MI patients. Statistically significant differences between MI<50 and MI≥50 groups as well as young healthy control group were revealed regarding prevalence of smoking, body mass index (BMI), LDL, HDL, triglycerides (TG) and glucose levels.Conclusions. Younger age of patients with myocardial infarction correlates with a higher number of relatives with a history of premature MI/ischemic stroke. Thus, the family history of premature atherosclerosis involving not only the first-, but also the second-degree relatives, seems to be valuable and could be considered in an individual CVD risk evaluation in young people.


2020 ◽  
Vol 7 (3) ◽  
pp. 446
Author(s):  
Venugopal Margekar ◽  
Shweta Thakur ◽  
O. P. Jatav ◽  
Pankaj Yadav

Background: A significant percent of cardiovascular event occurs without well-known modifiable risk. A new tool for early identification for atherosclerosis is required for early intervention. Aims and objectives of the study was to study the risk factors for CAD and its correlation with CIMT.Methods: One hundred and forty subjects were studied for the risk factors of CAD in Department of Medicine of G.R. Medical College, Gwalior from 2012 to 2013. Out of 140 subjects, 100 were patients having CAD and 40 age matched subjects were included as control group. Data was also recorded from their offspring. High resolution B mode ultrasonography was performed to assess CIMT of carotid arteries. The maximum CIMT of any one side of carotid artery was taken for study.Results: CAD was more prevalent among males (78%). Majority of the offspring of cases had age between 28-42 years and majority were male (73%). Most common risk factors for CAD was dyslipidemia (48%), hypertension (24%), diabetes (12%) and smoking (21%), whereas in offspring’s of CAD patients, dyslipidemia was seen in 28%, hypertension in 3%, diabetes and tobacco smoking in 12% and 24% respectively. The CIMT of CAD patients was significantly increased with increasing the number of risk factors and the same pattern was also seen in controls.  The CIMT of asymptomatic offspring’s having positive family history was significantly more than the asymptomatic offspring without positive family history of CAD.Conclusions: CIMT measurements can be used as a surrogate marker of atherosclerosis as it has showed a direct link with number of risk factors of CAD. 


2020 ◽  
Author(s):  
Ruifang Liu ◽  
Fangxing Xu ◽  
Yujie Zhou ◽  
Tongku Liu

Abstract Background In recent years, the prevalence rate of ACS in Chinese young women has been increasing significantly, becoming the main cause of death in young female. This study aimed to investigate the characteristics and difference of risk factors in Chinese young women with ACS and to provide references for ACS prevention and treatment. Methods A 1:1 case-control study was conducted to evaluate risk factors of 415 young female patients with ACS (ACS group) who underwent PCI treatment and 415 young female cases without ACS (control group) who were hospitalized and confirmed by coronary angiography to exclude coronary heart disease from January 2010 to August 2016. The average age of the cases in the two groups was respectively (40.77±4.02) years-old and (40.57±4.01) years-old (P> 0.05). Results The risk factors in ACS group were overweight (64.10%), hypertension (49.88%), hyperlipidemia (35.66%), diabetes (23.37%), depression or anxiety disorder (16.62%), gynecological diseases (16.39%), Hyperuricemia (15.18%), family history of early onset coronary heart disease (14.94%), hyperhomocysteinemia (11.33%), hypothyroidism(14.96%), hypercholesterolemia (8.43%) and high c-reactive protein (7.47%), and were statistically significant difference (P<0.01) compared with that of control group. The average number of risk factors per case in ACS group was significantly more than that of control groups (P<0.01). There was a statistically significant difference in the number of combined risk factors of the overweight cases compared between two groups (P<0.01). Regression analysis showed that hyperlipidemia, hyperhomocysteinemia, overweight(obesity), high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases were independent risk factors (P<0.01). The bivariate correlation analysis between CRP level and age was r= -0.158 (P<0.01). This result showed the younger ACS patient is the higher serum CRP. Conclusion The independent risk factors of ACS in young women are hyperlipidemia, hyperhomocysteinemia, overweight, high CRP, hypertension, hypothyroidism, gynecological diseases, depression or anxiety, cardiac insufficiency, hypercholesterolemia, diabetes, oral contraceptives, family history of early onset CHD, and autoimmune diseases. The co-existence of multiple risk factors is the main cause suffering from ACS in young women.


2021 ◽  
Author(s):  
Tiantian Wang ◽  
Fei Wang ◽  
Tingting Liu ◽  
Menghu Sun ◽  
Feimeng An ◽  
...  

Abstract Background and purpose: Alcohol-induced osteonecrosis of the femoral head (ONFH) is a complex and heterogeneous disease. Genetic factors and epigenetic modifications are one of the pathogenesis of the disease. However, the influence of epigenetic factors on the disease has not been systematically studied. Our research aims to determine the methylation changes of alcohol-induced ONFH.Methods:An analytical cross-sectional study of a Chinese male population (50 lung cancer patients and 50 controls). The EpiTYPER of the Sequenom MassARRAY platform was used to detect the DNA methylation status of 132 Cytosine-phosphate-Guanine (CpG) sites in the OPG/RANKL/RANK gene promoter region.Results: In the whole study group,Chi-square test was used to analyze the methylation rate between the two groups, and six CpG sites were found to be different, among which OPG1_CpG_2, OPG3_CpG_4, RANK1_CpG_6, RANK3_CpG_10, RANKL2_CpG_21, and RANKL2_CpG_46 in the case group were higher than those in the control group, while OPG4_CpG_2 was lower than that in the control group. Our results showed that 146 CpG sites were measured, of which 32 were undetectable, and of the remaining 114 methylation sites, methylation levels were different in 23 CpG sites in patients with alcohol-induced ONFH compared to healthy controls. Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of OPG/RANKL/RANK could efficiently predict the existence of alcohol-induced ONFH.Conclusion: Our study of Chinese men suggests that several CpG sites in the OPG/RANKL/RANK gene in peripheral blood leukocytes of patients with alcohol-induced ONFH are in abnormal methylation state(hypermethylation tended to be more frequent).


2019 ◽  
Vol 33 (12) ◽  
pp. 1550-1561 ◽  
Author(s):  
Maria Vittoria Micioni Di Bonaventura ◽  
Mariangela Pucci ◽  
Maria Elena Giusepponi ◽  
Adele Romano ◽  
Catia Lambertucci ◽  
...  

Background:Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited.Methods and aims:Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2AAdenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes.Results:Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.Conclusion:We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Ningyi Jia ◽  
Jian Li

Objective. The present study aimed to identify changes in decidual natural killer (dNK) cells and related cytokines in women who have undergone induced abortions (IAs). The effects of dNK cells on subsequent pregnancies remain unknown. Accordingly, we sought to investigate whether a history of early pregnancy can change dNK cells and facilitate their role in the regulation of angiogenesis and trophoblast invasion. Materials and Methods. dNK cells were obtained from primiparous women who had undergone IA(s) prior to this study and primiparous women who had never been pregnant before this IA (control). Real-time polymerase chain reaction (PCR) was used to measure the mRNA levels of IFN-γ, IP-10, VEGF, and PLGF in dNK cells. The levels of these cytokines were quantified using the enzyme-linked immunosorbent assay. HUVEC and HTR-8/SVneo cells were used to evaluate the angiogenesis, migration, and invasion activities influenced by dNK cells. Results. In dNK cells, the mRNA level of IFN-γ was higher in the control group than that in the IA group. The secretion of IP-10 and VEGF was higher in the IA group compared to the control group. After coculturing with the dNK supernatant, the HTR-8/SVneo cells exhibited better invasiveness and migration in the IA group than those in the control group. Angiogenesis assay demonstrated that dNK cells from IA group might help HUVEC attain better tube formation ability. Conclusion. The findings of this study suggest that a history of early pregnancy has an impact on dNK cells. These trained dNK cells can regulate angiogenesis and trophoblast invasion and migration by promoting the production of certain cytokines.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia Olaru ◽  
Smaranda Diaconescu ◽  
Laura Trandafir ◽  
Nicoleta Gimiga ◽  
Gabriela Stefanescu ◽  
...  

We conducted an observational study over a 1-year period, including 234 children aged 4–18 years and their caregivers and a matching control group. 60.73% of the children from the study group were males. Average age for the onset of constipation was 26.39 months. The frequency of defecation was 1/4.59 days (1/1.13 days in the control group). 38.49% of the patients in the sample group had a positive family history of functional constipation. The majority of children with functional constipation come from single-parent families, are raised by relatives, or come from orphanages. Constipated subjects had their last meal of the day at later hours and consumed fast foods more frequently than the children in the control sample. We found a statistically significant difference between groups regarding obesity/overweight and constipation (χ2=104.94,  df=2,  p<0.001) and regarding physical activity and constipation (χ2=18.419;  df=3;  p<0.001). There was a positive correlation between the number of hours spent watching television/using the computer and the occurrence of the disease (F= 92.162,p<0.001, and 95% Cl). Children from broken families, with positive family history, defective dietary habits, obesity and sedentary behavior, are at higher risk to develop chronic functional constipation.


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