Incidence of breast cancer and methylation of PCDH gene: a single ratio meta analysis of single rate

IntroductionBreast cancer presents one of the highest rates of prevalence. With the development of genetics and biotechnology, we have learned that the occurrence and development of many cancers are closely related to abnormal gene expression. At present, some pieces of literature have reported that there may be a correlation between the expression of PCDH and the occurrence of breast cancer.Therefore, we selected some loci from PCDH gene to explore the correlation between the methylation of PCDH gene and breast cancer.Material and methodsThis research is a systematic review and critical appraisal, make a meta-analysis of prospective and retrospective cohort study. Research was conducted through computer Science, Wanfang and Chinese knowledge network databases PubMed, Embase and Network. In a literature search, seven cohort studies were identified. This I2 statistic is used to quantify heterogeneity. A fixed effect model was used to synthesize the results. Regression tests of linear funnel plot asymmetry were used to estimate potential publication bias.ResultsThe methylation rate of PCDH gene in breast cancer with lymph node metastasis was 75%, and that in breast cancer without lymph node metastasis was 70%. The methylation rate of PCDH gene was 75% in breast cancer group with high expression of the Ki-67 gene and 71% in breast cancer group with low expression of Ki-67 gene.ConclusionsAccording to previous studies, the positive rate of methylation of PCDH gene in breast cancer tissues is higher than that in adjacent tissues, and there is no obvious statistical difference in the correlation between lymphatic metastasis and Ki-67.

Alteration of serum leptin and LEP/LEPR promoter methylation in Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed but maternally imprinted genes in chromosome region 15q11-13. During child development, PWS usually results in insatiable appetite with subsequent obesity representing the major mortality factor. The neurobiological basis of PWS-typical hyperphagia has remained poorly understood. Many PWS-typical abnormalities are based on hypothalamic dysregulation, the region in which hunger and satiety are hormonally regulated, with the hormone leptin being a main long-term regulator of satiety. Previous studies in PWS have inconsistently shown leptin alterations solely in early childhood, without investigating the leptin system on an epigenetic level. The present study investigates serum leptin levels (S-leptin) and methylation of the leptin (LEP) and leptin receptor gene (LEPR) promoter in 24 individuals with PWS compared to 13 healthy controls matched for sex, age, and body mass index (BMI) and relates the results to the extent of hyperphagia in PWS. S-Leptin levels were obtained by Enzyme-linked Immunosorbent Assay. LEP/LEPR-promoter methylation was assessed by DNA-bisulfite-sequencing, hyperphagia by Hyperphagia Questionnaire for Clinical Trials (HQ-CT). PWS and control groups differed significantly in S-leptin levels with higher S-leptin in PWS. Methylation analysis showed significant differences in mean promoter methylation rate both for LEP and LEPR with a lower methylation rate in PWS. LEPR, but not LEP methylation correlated with S-leptin levels. S-leptin and both LEP and LEPR methylation did not correlate with HQ-CT scores in PWS. The present study is the first to show significantly elevated S-leptin levels in an adult PWS cohort combined with an altered, downregulated LEP and LEPR promoter methylation status compared to BMI-matched controls. Analogous to previous studies, no link to the behavioral dimension could be drawn. Overall, the results suggest an increased leptin dysregulation in PWS, whereby the findings partly mirror leptin resistance seen in non-syndromic obesity.

Hypomethylation of Monoamine Oxidase A promoter/exon 1 region is associated with temper outbursts in Prader-Willi syndrome

Background: Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2-13. It is associated with a certain behavioural phenotype with repetitive and ritualistic behaviours, skin-picking and temper outbursts. Temper outbursts are characterized by verbal and physical aggression with screaming, destroying property, and/or physical aggression towards others. They drastically effect the quality of life of the individuals as well as the relatives and caregivers. Recent studies show a promising therapeutic effect of serotonin reuptake inhibitors like sertraline on frequency and intensity of outbursts. Monoamine oxidase A (MAOA) (X p11.23) plays a crucial role in the metabolism of monoamines such as serotonin, norepinephrine, and dopamine. Dysregulation in methylation of the CpG island spanning the promoter region and exon 1 of MAOA is implicated in impulsive and aggressive behaviour. Methods: In the present study, methylation rates of CpG dinucleotides in the MAOA promoter and exon 1 region were determined from DNA derived from whole blood samples of PWS patients (n=32) and controls (n=14) matched for age, sex and BMI via bisulfite sequencing. PWS patients were grouped into those showing temper outbursts, and those who do not. Results: Overall, PWS patients show a significant lower methylation rate at the promoter/exon 1 region than healthy controls in both sexes. Furthermore, PWS patients, male as well female with temper outbursts show a significant lower methylation rate than those without temper outbursts (p<0.001 and p=0.006) Conclusion: The MAOA promoter/exon 1 region methylation seems to be dysregulated in PWS patients in sense of a hypomethylation, especially in those suffering from temper outbursts. As MAOA is involved in the metabolism of serotonin, we conclude that this dysregulation plays a crucial role in the pathophysiology of temper outbursts in PWS. Furthermore, our findings suggest, that dysregulation of certain genes outside the PWS locus contribute to the behavioural phenotype of PWS.

The evaluation for CpG island methylation of FASN and SREBP promoter in Mongolian gerbils NAFLD model

IntroductionThe methylation of CpG island in promoter and its nearby area is one of the most important way to inhibit gene expression. The aim of this study was to examine the potential relationship between the CpG island methylation for fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP-1).Material and methodsTen newborn pups of gerbils as NB group, 10 adult gerbils with normal diet as control group, 10 adults with high-fat diet as NAFLD group, and 10 8-month-old as aged group. Blood and liver samples were collected for serum lipid detection and histopathology. A pyrosequencing technique was employed to determine the methylation rate. Then, the transcription and expression level for FASN and SREBP-1 were verified.ResultsSerum chelosterol and triglyceride was significantly increased in NAFLD and aged group (vs. control, P<0.05). The gerbils in NAFLD and aged group also showed obvious hepatic steatosis confirmed by histological examination. Control group had the highest methylation rate for FASN and SREBP-1, which were reduced in NAFLD and aged group. Except for NB group, both the transcription and expression levels of SREBP-1 and FASN genes were presented control group> Aged group > NAFLD group. Genes of SREBP and FASN showed a trend of hypomethylation in the NAFLD gerbil model.ConclusionsThe expression of SREBP gene tended to decrease, while the expression of FASN gene tended to increase with the age and disease development. FASN and SREBP-1 methylation might be a new method to evaluate NAFLD animal model and an available target for genetic marker screening.

Effects of 24-Epibrassinolide on DNA Methylation Variation in Soybean (Glycine max) Leaf and Root Under Saline-Alkali Stress

Saline-alkali stress is major stress that severely reduces plant growth and productivity, it is necessary to make clear whether exogenous 24-epibrassinolide (EBR) can improve the salt-alkali resistance of soybean (Glycine max) by affecting its DNA methylation. In this study, the effects of EBR on soybean adaptation to saline-alkali stress, genomic DNA methylation level and pattern changes in saline-alkali-stressed leaf and root with or without EBR treatment were compared using methylation-sensitive amplified polymorphism (MSAP). In the results, saline-alkali stress increased DNA methylation levels in leaf and root, with higher respective hemi-methylation and global methylation rates observed in leaf (6.22, 22.24%) than root (5.72, 21.76%). EBR application reduced leaf and root DNA methylation levels, with leaf hemi-methylation rate (6.15%) exceeding that of root (4.25%) and leaf global methylation rate (21.79%) below that of root (22.51%). There were distinct DNA remethylation and demethylation variations across different tissues and treatments, demethylation in leaves was dominant. Meanwhile, untreated saline-alkali-stressed roots exhibited major demethylation-based variations, while remethylation variations predominated post-treatment. Under saline-alkali stress, root remethylation and demethylation rates (6.17, 7.55%, respectively) both exceeded respective leaf rates (5.18 and 7.46%); however, post-EBR treatment, root methylation rate (6.45%) exceeded leaf rate (5.38%), while root demethylation rate (6.13%) fell below leaf rate (6.94%). In conclusion, exogenous EBR application to saline-alkali-stressed soybean can influence leaf and root genomic DNA methylation levels and patterns via distinct tissue-specific methylation mechanisms.

Methylation of TGM-3 Promoter and Its Association with Oral Squamous Cell Carcinoma (OSCC)

Background: Oral Squamous Cell Carcinoma (OSCC) is among the ten most common cancers worldwide. Hypermethylation of CpG sites in the promoter region and subse-quent down-regulation of a tumor suppressor gene, TGM-3 has been proposed to be linked to different types of human cancers including OSCC. In this study, methylation sta-tus of CpG sites in the promoter region of TGM-3 has been evaluated in a cohort of pa-tients with OSCC compared to normal controls. Methods: Forty fresh tissue samples were obtained from newly diagnosed OSCC patients and normal individuals referred to dentistry clinic for tooth extraction. DNA was extract-ed, bisulfite conversion was performed and it was subjected to PCR using bisulfite-sequencing PCR (BSP) primers. Prepared samples were sequenced on a DNA analyzer with both forward and reverse primers of the region of interest. The peak height values of cytosine and thymine were calculated and methylation levels for each CpG site within the DNA sequence was quantified. Results: Quantitative DNA methylation analyses in CpG islands revealed that it was sig-nificantly higher in OSCC patients compared to controls. DNA methylation at CpG1/CpG3/CpG5 (p=0.004-0.01) and CpG1/CpG3 (p=0.001-0.019) sites was associated with tumor stage and grade, respectively. Male OSCC patients had higher methylation rate at CpG3 (p=0.032), while smoker patients showed higher methylation rate at CpG6 (p=0.045). Conclusion: These results manifested the contribution of DNA methylation of TGM-3 in OSCC and its potential association with clinico-pathologic parameters in OSCC.

Genetic Determinism Exists for the Global DNA Methylation Rate in Sheep

Recent studies showed that epigenetic marks, including DNA methylation, influence production and adaptive traits in plants and animals. So far, most studies dealing with genetics and epigenetics considered DNA methylation sites independently. However, the genetic basis of the global DNA methylation rate (GDMR) remains unknown. The main objective of the present study was to investigate genetic determinism of GDMR in sheep. The experiment was conducted on 1,047 Romane sheep allocated into 10 half-sib families. After weaning, all the lambs were phenotyped for global GDMR in blood as well as for production and adaptive traits. GDMR was measured by LUminometric Methylation Analysis (LUMA) using a pyrosequencing approach. Association analyses were conducted on some of the lambs (n = 775) genotyped by using the Illumina OvineSNP50 BeadChip. Blood GDMR varied among the animals (average 70.7 ± 6.0%). Female lambs had significantly higher GDMR than male lambs. Inter-individual variability of blood GDMR had an additive genetic component and heritability was moderate (h2 = 0.20 ± 0.05). No significant genetic correlation was found between GDMR and growth or carcass traits, birthcoat, or social behaviors. Association analyses revealed 28 QTLs associated with blood GDMR. Seven genomic regions on chromosomes 1, 5, 11, 17, 24, and 26 were of most interest due to either high significant associations with GDMR or to the relevance of genes located close to the QTLs. QTL effects were moderate. Genomic regions associated with GDMR harbored several genes not yet described as being involved in DNA methylation, but some are already known to play an active role in gene expression. In addition, some candidate genes, CHD1, NCO3A, KDM8, KAT7, and KAT6A have previously been described to be involved in epigenetic modifications. In conclusion, the results of the present study indicate that blood GDMR in domestic sheep is under polygenic influence and provide new insights into DNA methylation genetic determinism.

Association between SIRT6 Methylation and Human Longevity in a Chinese Population

<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>_s = −0.173, <i>p</i> = 0.011) and P5 sites (<i>r</i>_s = −0.207, <i>p</i> = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (<i>r</i>_s = 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.

The lower methylation of RANK is associated with osteoporosis in male aged general population of Xinjiang: A Case-Control Study

Background RANK is a candidate gene for osteoporosis on both functional and genetic grounds. The study is to investigate the relationships between the methylation of RANK and osteoporosis in aged general population. Methods On the basis of an epidemiological investigation, we detect for methylation CpGs in promoter of RANK in 32 aged subjects (16 males and 16 females) firstly. Secondly, after considering the relationships among osteoporosis and the methylation rate of identified CpGs in male and female subjects, the selected representatives CpGs were detected in 90 male aged general subjects (43 controls and 47 cases) by bisulfite sequencing. Then a case-control study is conducted. Results Age and the prevalence of diabetes were significantly difference between the case patients and control individuals (P = 0. 025, P = 0. 005)., There was no statistical significance between the case group and the control group for the following values: systolic blood pressure, diastolic blood pressure, body mass index, 25-dihydroxyvitaminD3, folic acid, testosterone, creatinine, serum calcium concentration, and the prevalence of smoking, drinking and hypertension (P > 0.05). The methylation rate of RANK in control group was significant higher than that in osteoporosis group (P < 0.001). In addition, by covariance analysis to adjust age, prevalence of smoking, drinking, hypertension, and diabetes, the methylation rate of RANK in control group was significant higher than that in osteoporosis group in male aged general population of Xinjiang (P = 0.001). After adjusting for confounding factors (age, smoking, drinking, and diabetes), multivariate logistic regression analysis also showed that lower methylation of RNAK gene were significantly associated with osteoporosis (OR = 0.930, 95% CI = 0.886–0.976) Conclusions The lower methylation rate of RANK was associated with osteoporosis in male aged general population of Xinjiang. This confirms that lower methylation of RANK might be involved in the pathogenesis of osteoporosis