超重孕妇低生糖负荷膳食干预对新生儿DNA甲基化影响的探索性研究

目的通过对超重孕妇实施低血糖生成指数(GI)膳食的干预,探讨胎盘组织和脐血中与体重增长有关基因的甲基化的改变。 方法采用随机化单盲对照干预试验设计,研究对象为初次产检孕周≤12周且体重超重的孕妇。以研究对象纳入的顺序号为随机序列号,采用简单随机化的方法随机分为干预组和对照组。干预组在中国孕妇保健规范的基础上结合国家对孕妇的膳食和体力活动规范实施低GI膳食指导干预 ,对照组仅按照国家规范给予指导,不给予低GI膳食的指导。两组分别在孕早期、中期和晚期干预3次。 干预组和对照组各纳入25例。孕妇分娩时收集胎盘组织和脐血,提取DNA,采用Illumina甲基化芯片进行两步法全基因组甲基化测定。 结果孕妇孕期相关暴露因素在干预组与对照组差异无统计学意义;胎儿出生体重干预组高于对照组［（3.7±0.5） vs (3.5±0.4) kg］,但差异无统计学意义(P=0.248)。本研究结果结合生物信息数据库分析,筛选出19个基因位点,所属18个基因,其中5个基因位于1号染色体,2个基因位于7号染色体,其余基因分布分散。比较干预组与对照组甲基化的改变,发现脐血中2个差异的甲基化CpG位点,分别位于TEKT5和MIR378C基因上,胎盘组织中1个差异的甲基化CpG位点,所属PGBD5基因。 结论通过对超重孕妇采取低GI膳食干预,胎盘组织和脐血中基因的甲基化可以发生改变,为中国超重、肥胖孕妇疾病的预防提供新的方法,对子代的健康成长有重要的意义。     

Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

Background:The diagnosis of myelodysplastic syndrome (MDS),especially hypoplastic MDS,and MDS with low blast counts or normal karyotype may be problematic.This study characterized ID4 gene methylation ...     

Blood-based DNA methylation of DNA repair genes in the non-homologous end-joining (NEHJ) pathway in patient with glioma

To investigate the blood-based DNA methylation of repair genes including LIG4, XRCC4, XRCC5, XRCC6 and XRCC7 that involved in non-homologous end-joining (NEHJ) DNA repair pathway in patients with glioma. Blood samples were obtained from 114 glioma patients, 96 normal controls, and 81 glioma patients after radiotherapy and chemotherapy. Blood-based DNA methylation of the five NHEJ repair genes was assayed by methylation-specific polymerase chain reaction (MSP). The DNA methylation level of XRCC5 and XRCC7 in glioma group are significantly higher than those of normal group (P<0.001). Moreover, radiotherapy treatment significantly increased methylation level of XRCC5 and XRCC7 compared to glioma group. No significant difference for the methylation of the other three genes, LIG4, XRCC4 and XRCC6 were detected among three groups. In conclusion: our findings indicate that DNA methylation modification plays an important role to regulate the gene expression of XRCC5 and XRCC7, from the results that the gene methylation level of the glioma group is higher than that of the normal group. Increased methylation of XRCC5 and XRCC7 in blood samples of glioma patients and patients with radiotherapy and chemotherapy suggests that blood-based methylation level of XRCC5 and XRCC7 could be a potential indicator for evaluating of the effect of radiotherapy and chemotherapy for glioma patient.     

Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype

The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects – mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.     

表观遗传学和环境因素与子宫内膜异位症

子宫内膜异位症(EMs)是一种雌激素依赖的炎性疾病,发病机制尚不清楚。越来越多的证据表明,一些基因的表观遗传学特性与EMs的发病有关。表观遗传学是指DNA序列不发生变化,但基因表达却发生了可遗传的改变,包括DNA甲基化、组蛋白共价修饰及染色质构象变化,这些改变可能会引发一系列包括肿瘤在内的病理变化。EMs异位组织中芳香化酶基因的Cp G岛序列低甲基化和(或)反式作用因子上调芳香化酶基因的表达;卵巢异位上皮及间质细胞的雌激素受体α(ERα)低表达而ERβ显著高表达;在位细胞的孕激素受体α(PRα)和PRβ均高表达;EMs异位内膜细胞的类固醇生成因子1(SF-1)启动子低甲基化而在位内膜高甲基化。此外,EMs异位组织E-钙黏蛋白(E-cadherin)基因及在位组织同源框基因A10(HOXA10)表达降低也与EMs有关;环境因素可能会影响表观遗传基因导致EMs的发生。综述表观遗传学改变和环境因素在EMs发病中的作用。     

DNA methylation changes in the placenta are associated with fetal manganese exposure

Adequate micronutrient intake, including manganese (Mn), is important for fetal development. Both Mn deficiencies and excess exposures are associated with later-life disease, and Mn accumulates in the placenta. Placental functional alterations may alter fetal programming and lifelong health, and we hypothesized that prenatal exposures to Mn may alter placental function through epigenetic mechanisms. Using Illumina's HumanMethylation450 BeadArray, DNA methylation of >485,000 CpG loci genome-wide was interrogated in 61 placental samples and Mn associations assessed genome-wide via omnibus test (p = 0.045). 713 loci were associated with Mn exposure (p < 0.0001). Five significantly differentially-methylated (p < 1.3 × 10⁻⁷) loci reside in neurodevelopmental, fetal growth and cancer-related genes. cg22284422, within the uncharacterized LOC284276 gene, was associated with birth weight; for every 10% increase in methylation, lower birth weights were observed, with an average decrease of 293.44 g. Our observations suggest a link between prenatal micronutrient levels, placental epigenetic status and birth weight, although these preliminary results require validation.     

DDX43基因与肿瘤

DEAD盒多肽43(DDX43)基因在肿瘤细胞恶性增殖、肿瘤细胞耐药及肿瘤免疫治疗方面发挥着重要作用.DDX43基因在多种实体瘤和某些血液系统恶性肿瘤中表达增高.DDX43基因启动子低甲基化出现于慢性髓系白血病、急性髓系白血病和骨髓增生异常综合征,并且与DDX43高表达和疾病的预后相关.     

DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C,and TRIM59 genes for age prediction from blood,saliva, and buccal swab samples

Many studies have reported age-associated DNA methylation changes and age-predictive models in various tissues and body fluids. Although age-associated DNA methylation changes can be tissue-specific, a multi-tissue age predictor that is applicable to various tissues and body fluids with considerable prediction accuracy might be valuable. In this study, DNA methylation at 5 CpG sites from the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes were investigated in 448 samples from blood, saliva, and buccal swabs. A multiplex methylation SNaPshot assay was developed to measure DNA methylation simultaneously at the 5 CpG sites. Among the 5 CpG sites, 3 CpG sites in the ELOVL2, KLF14 and TRIM59 genes demonstrated strong correlation between DNA methylation and age in all 3 sample types. Age prediction models built separately for each sample type using the DNA methylation values at the 5 CpG sites showed high prediction accuracy with a Mean Absolute Deviation from the chronological age (MAD) of 3.478 years in blood, 3.552 years in saliva and 4.293 years in buccal swab samples. A tissue-combined model constructed with 300 training samples including 100 samples from each blood, saliva and buccal swab samples demonstrated a very strong correlation between predicted and chronological ages (r = 0.937) and a high prediction accuracy with a MAD of 3.844 years in the 148 independent test set samples of 50 blood, 50 saliva and 48 buccal swab samples. Although more validation might be needed, the tissue-combined model’s prediction accuracies in each sample type were very much similar to those obtained from each tissue-specific model. The multiplex methylation SNaPshot assay and the age prediction models in our study would be useful in forensic analysis, which frequently involves DNA from blood, saliva, and buccal swab samples.