scholarly journals Epigenome-wide analysis of DNA methylation and coronary heart disease: a nested case-control study

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jiahui Si ◽  
Songchun Yang ◽  
Dianjianyi Sun ◽  
Canqing Yu ◽  
Yu Guo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
Methylation Level ◽  
Case Control Study ◽  
Asian Population ◽  
Cpg Sites ◽  
Chd Risk ◽  
Nested Case Control ◽  
Control Study

Background: Identifying environmentally responsive genetic loci where DNA methylation is associated with coronary heart disease (CHD) may reveal novel pathways or therapeutic targets for CHD. We conducted the first prospective epigenome-wide analysis of DNA methylation in relation to incident CHD in the Asian population.Methods: We did a nested case-control study comprising incident CHD cases and 1:1 matched controls who were identified from the 10-year follow-up of the China Kadoorie Biobank. Methylation level of baseline blood leukocyte DNA was measured by Infinium Methylation EPIC BeadChip. We performed the single cytosine-phosphate-guanine (CpG) site association analysis and network approach to identify CHD-associated CpG sites and co-methylation gene module.Results: After quality control, 982 participants (mean age 50.1 years) were retained. Methylation level at 25 CpG sites across the genome was associated with incident CHD (genome-wide false discovery rate [FDR] < 0.05 or module-specific FDR <0.01). One SD increase in methylation level of identified CpGs was associated with differences in CHD risk, ranging from a 47% decrease to a 118% increase. Mediation analyses revealed 28.5% of the excessed CHD risk associated with smoking was mediated by methylation level at the promoter region of ANKS1A gene (P for mediation effect = 0.036). Methylation level at the promoter region of SNX30 was associated with blood pressure and subsequent risk of CHD, with the mediating proportion to be 7.7% (P = 0.003) via systolic blood pressure and 6.4% (P = 0.006) via diastolic blood pressure. Network analysis revealed a co-methylation module associated with CHD.Conclusions: We identified novel blood methylation alterations associated with incident CHD in the Asian population and provided evidence of the possible role of epigenetic regulations in the smoking- and BP-related pathways to CHD risk.Funding: This work was supported by National Natural Science Foundation of China (81390544 and 91846303). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), grant (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key and Program of China, and Chinese Ministry of Science and Technology (2011BAI09B01).

scholarly journals Early Pregnancy Peripheral Blood DNA Methylation and Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study

2021 ◽  
Author(s):  
Xiaolei Wang ◽  
Jin Huang ◽  
Sisi Long ◽  
Huijun Lin ◽  
Na Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Peripheral Blood ◽  
Case Control Study ◽  
Methylation Status ◽  
First Trimester ◽  
Case Control ◽  
Cpg Sites ◽  
Nested Case Control ◽  
Control Study

Abstract Introduction: Genome-wide DNA methylation profiling has been used to identify CpG sites relevant to gestational diabetes mellitus (GDM). However, these sites have not been verified in larger samples. Here, our aim was to evaluate the changes in target CpG sites in the peripheral blood of pregnant women with GDM in their first trimester. Research Design and Methods: This nested case-control study examined a large cohort of women with GDM in early pregnancy (10–15 weeks; n = 80). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites located in 27 target genes were determined using MethylTarget™ sequencing. The best cut-off levels for methylation of CpG sites were determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Results Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at 7 CpG sites were significantly lower (P < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for GDM prediction. After adjusting for possible confounders, the hypermethylation status of candidate sites cg68167324 (OR = 3.168, 1.038–9.666) and cg24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; conversely, the hypermethylation of sites cg157130156 (OR = 0.361, 0.135–0.966) and cg89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. Conclusions The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester is associated with GDM pathogenesis, and has potential as a predictor of GDM.

Genetic analysis of DNA methylation in dyslipidemia: a case-control study

2020 ◽  
Author(s):  
Yi-Tong Ma ◽  
Shuai Liu ◽  
Yang Li ◽  
Xian Wei ◽  
Dilare Adi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Cpg Sites ◽  
Heart Center ◽  
Medical University ◽  
The Relationship ◽  
Control Study

Abstract In our previous study, we explored the relationship between TBL2 gene DNA methylation and high-low-density lipoproteinemia (Hyper-LDL). However, Hyper-LDL is only one type of dyslipidemia. In order to expand the scope of clinical application, we explored the correlation between DNA methylation of genes related to lipid metabolism and dyslipidemia in this study. This study is a case-control study. A total of 180 samples were included in this study from the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. The BSAS method was used to detect the DNA methylation levels and haplotypes of AMFR, FBXW7, INSIG1, INSIG2, MBTPS1 and GRINA genes. A total of 259 CpG sites and 14 regions were detected. The study found that a total of 24 CpG sites DNA methylation and 20 haplotypes were statistically different. The GRINA gene DNA methylation level in the dyslipidemia group was higher than that in the control group (2.68 vs 2.36, p = 0.04). ttttttttttttcttttttttttt is significant methylation haplotype of GRINA (p=0.017). Through logistics analysis, it is found that GRINA gene DNA methylation is an independent risk factor for dyslipidemia, and the increase of GRINA gene DNA methylation level will increase the prevalence of dyslipidemia.

DNA Methylation in Peripheral Blood and Risk of Gastric Cancer: A Prospective Nested Case–control Study

2020 ◽  
Author(s):  
James A Chamberlain ◽  
Pierre-Antoine Dugué ◽  
Julie K. Bassett ◽  
Roger L. Milne ◽  
Jihoon E Joo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Peripheral Blood ◽  
Case Control Study ◽  
Case Control ◽  
Nested Case Control ◽  
Control Study

scholarly journals Determinants of adherence to anti-hypertensive medications among adult hypertensive patients on follow-up in Hawassa Referral Hospital: A case–control study

2019 ◽  
Vol 8 ◽  
pp. 204800401989275
Author(s):  
Atsede Getenet ◽  
Mulugeta Tesfa ◽  
Aster Ferede ◽  
Yalew Molla
Keyword(s):  
Blood Pressure ◽  
Logistic Regression ◽  
Medication Adherence ◽  
Case Control Study ◽  
Case Control ◽  
Referral Hospital ◽  
Hypertensive Patients ◽  
Adherence Scale ◽  
Control Study

Introduction Hypertension is a global challenge which accounts for high morbidity and mortality rates in the world. The availability of effective anti-hypertensive medications does not result in a good outcome in controlling blood pressure which points towards poor adherence. Thus, this study was conducted to assess the determinants of adherence to anti-hypertensive medication among hypertensive patients on follow-up in Hawassa Referral Hospital. Methods Institution-based case–control study was conducted on a sample of 289 clients from February to May 2018. Census was conducted on 1600 clients to select cases and controls. Then, systematic random sampling was used to select study subjects, and adherence was measured by Morisky medication adherence scale. The associations of variables were analyzed using bivariable followed by multivariable logistic regression analyses. Results The respondent’s adherence to medication was found to be 67% as measured by Morisky medication adherence scale. The multivariate logistic regression analysis showed that medication adherence was found to be better in younger age (<45) (AOR = 3.8), clients living in urban areas (AOR = 6.84), those clients who had good knowledge (AOR = 3.13), those with no co-morbidities (AOR = 3.14) and patients who controlled their blood pressure (<140/90) (AOR = 2.35). Conclusions The rate of medication adherence was found to be low, and hence educational interventions focusing on factors promoting adherence and patients’ health support should be implemented.

Risk Factors for Tuberculosis (TB) Among Household Contacts of Patients With Smear-Positive TB in 8 Provinces of Vietnam: A Nested Case-Control Study

2020 ◽  
Author(s):  
Kavindhran Velen ◽  
Nguyen Viet Nhung ◽  
Nguyen Thu Anh ◽  
Pham Duc Cuong ◽  
Nguyen Binh Hoa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Case Control Study ◽  
Factors Associated ◽  
Household Contacts ◽  
Key Population ◽  
History Of ◽  
Nested Case Control ◽  
And Control ◽  
Control Study

Abstract Background Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention and control interventions. We aimed to identify risk factors associated with developing TB among HHCs. Methods We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs. Results We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.03–2.0), residing in an urban setting (aOR, 1.8; 1.3–2.5), prior TB (aOR, 4.6; 2.5–8.7), history of diabetes (aOR, 3.1; 1.7–5.8), current smoking (aOR, 3.1; 2.2–4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1–2.3). Conclusions Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.

scholarly journals Methylation analysis of NPTX2 and SH2D5 genes in chronic migraine: A case–control study

2020 ◽  
Vol 3 ◽  
pp. 251581632092359
Author(s):  
Sara Pérez Pereda ◽  
María Toriello Suárez ◽  
Vicente González Quintanilla ◽  
Agustín Oterino
Keyword(s):  
Chronic Migraine ◽  
Methylation Level ◽  
Case Control Study ◽  
Epigenetic Modification ◽  
Case Control ◽  
Sh2 Domain ◽  
Upstream Region ◽  
Cpg Sites ◽  
Neuronal Pentraxin ◽  
Control Study

Background: Methylation of two CpG sites related to neuronal pentraxin II protein (NPTX2) and SH2 domain containing 5 protein (SH2D5), corresponding to two neuroplasticity genes, has been associated to headache chronification. We aimed to investigate the epigenetic modification of these two genes in chronic migraine (CM). Methods: We conducted a case–control study in which the DNA of 305 age- and sex-matched subjects classified according to the International Classification of Headache Disorders version beta (ICHD-III β) in CM (109), episodic migraine (EM; n = 98), and healthy controls (HC; 98) was analyzed. Real-time quantitative methylation-specific PCR was performed using specific methylation primers for two representative CpG sites within these genes. Results: We found no significant differences in methylation level between CM, EM, and HC in the first exon of the NPTX2 gene nor in the 5′ upstream region of the SH2D5 gene. Methylation level in the first exon of the NPTX2 showed a low correlation with age ( r = 0.266; p < 0.005). Conclusion: We did not find methylation level differences in analyzed regions related to NPTX2 and SH2D5 in our CM sample. Despite the potential relevance of neuroplasticity genes in headache chronification, we conclude that CM is a more heterogeneous clinical diagnosis than desired and that an epigenetic marker remains elusive.

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