Promoter methylation in coagulation F7 gene influences plasma FVII concentrations and relates to coronary artery disease

ABSTRACT. Maternal post-traumatic stress disorder (PTSD) increases the risk of adverse neurodevelopmental outcomes in the child. Epigenetic alternations may play an essential role in the negative effects of PTSD. This study was aimed to investigate the possible epigenetic alterations of maternal PTSD, which underpins the developmental and behavioral impact. 24 pregnant Sprague-Dawley (SD) rats were randomly grouped into PTSD and control groups. Open-field tests (OFTs), elevated pull maze (EPM) assays, gene expression profile chip tests, and methylated DNA immunoprecipitation sequencing (MeDIPSeq) were performed on the offsprings 30 days after birth. The results 2 X.G. Zhang et al. Genetics and Molecular Research 15 (3): gmr.15039009 showed that PTSD offsprings had lower body weights and OFT scores than control offsprings. Enzyme-linked immunosorbent assays showed that serotonin receptor (5-HT) and dopamine levels were significantly lower in PTSD offsprings than in control offsprings. In contrast, corticosterone levels were higher in the PTSD group than in the control group. In a comparison of the PTSD group versus the control group, 4,160 significantly differentially methylated loci containing 30,657 CpGs were identified; 2,487 genes, including 13 dysmethylated genes, were validated by gene expression profiling, showing a negative correlation between methylation and gene expression (R = -0.617, P = 0.043). In conclusion, maternal PTSD could delay the physical and behavioral development of offsprings, and the underlying mechanism could contribute to changes in neurotransmitters and gene expression, owing to dysregulation of wholegenome methylation. These findings could support further clinical research on appropriate interventions for maternal PTSD to prevent methylation dysregulation and developmental retardation.

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanism of maternal post-traumatic stress disorder in delayed rat offspring development: dysregulation of methylation and gene expression

X-G

Zhang

et al. 2016

“…Several studies have examined these polymorphisms in patients with venous and arterial thrombosis, but the results are very variable and sometimes contradictory (Athanasiadis et al, 2010;Lopaciuk et al, 2010;Eroğlu et al, 2010Eroğlu et al, , 2011Previtali et al, 2011;Friso et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis

Evangelista¹,

Rios²,

Ribeiro³

et al. 2015

ABSTRACT. Recent studies have shown an association between thrombosis and factor VII (FVII), tissue factor (TF), and angiotensinconverting enzyme (ACE). This suggests that individuals with FVII-402 G/A, FVII-401 G/T, TF+5466 A/G, and ACE-287 insertion/ deletion (I/D) polymorphisms present an increased risk of venous thrombosis, heart disease, and ischemic stroke compared with controls. In this study, we investigated the frequencies of these polymorphisms and their association with arterial and venous thrombosis. For the FVII-402 G/A polymorphism, there were 57.3% heterozygote (HT) genotypes and 8.3% homozygote (HM) genotypes in the patients, and 45.2% HT genotypes and 15.4% HM genotypes in the controls. For the FVII-401 G/T polymorphism, there were 37.5% HT genotypes and 3.1% HM genotypes in the patients, and 32.7% HT genotypes and 4.8% HM genotypes in the controls. The polymorphism TF+5466 A/G was not found in any of the samples analyzed. For the ACE-287 I/D polymorphism, there were 43 (40.6%) HT genotypes and 63 (59.4%) HM genotypes in the controls and 28 (45.2%) HT genotypes and 34 (54.8%) HM genotypes in the patients. No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.

“…With the rapid development of molecular biology technology, scientists have found many gene polymorphisms closely related to coronary heart disease susceptibility, such as those of angiotensin converting enzyme (Cambien et al, 1992;Narne et al, 2012), apolipoprotein (Hsu et al, 2006;Jang et al, 2009;Huang et al, 2012), cell factor (Zhong et al, 2009;Fragoso et al, 2010;Jin et al, 2012;Srikanth Babu et al, 2012), coagulation system (Pegoraro, 2005;Friso et al, 2012), and endothelin (Popov et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

MKL1-184C>T gene polymorphism is associated with coronary artery disease in the Chinese Han population

Bao

et al. 2014

ABSTRACT. We investigated genetic susceptibility to coronary artery disease (CAD) by studying the association of MKL1 gene polymorphisms with CAD in the Chinese Han population. We performed a case-control study with 476 unrelated CAD patients and 325 non-CAD controls. All SNPs were genotyped with a TaqMan SNP genotyping assay. The distribution of MKL1-184C>T gene polymorphism in each group was in Hardy-Weinberg equilibrium. The frequency of the MKL1 T allele in the CAD group was significantly higher than in the control group (38.6 vs 30.8%). After logistic regression models adjusted for CAD risk factors, the risk of CAD among CT genotypes was 1.765 times higher than among the CC genotypes [odds ration (OR) = 1.765, 95% confidence interval (CI) = 1.246-2.5], and for TT genotypes it was 1.806 times higher than for the CC genotypes (OR = 1.806, 95%CI = 1.203-2.71). In summary, genotypes with at least one T allele (CT or TT genotypes) had a significantly increased CAD risk than the CC genotypes, with a ratio of 1.78 to 1 (OR = 1.780, 95%CI = 1.311-2.418). There was a close association between -184 T allele and 3VD (OR = 1.614, 95%CI = 1.259-2.07, P < 0.05). We conclude that the -184C>T of MKL1 is an important susceptibility factor for CAD in the Han Chinese in Henan Province. Homozygosity for the T allele is not only associated with an increased risk for CAD, it is also correlated with severity of stenosis in the Chinese Han population.