Effect of epigenetics on vitamin D levels: a systematic review until December 2020.

BACKGROUND: The association between epigenetic modification of the genes involved in the vitamin D metabolic pathway and vitamin D metabolites' status has been elucidated incompletely. This study aims to review the studies on the mentioned association and create a brighter view of this topic. METHODS: A systematic literature search was conducted in Medline database (PubMed), Scopus, and Web of Science up to the end of November 2020. Original articles which reported the effect of epigenetic alteration-methylation level or its changes-of genes involved in vitamin D regulation on the vitamin D metabolites serum level or its changes were included. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. RESULTS: Among 2566 records, nine reports were included in the systematic review according to the inclusion and exclusion criteria. Studies discussed the contribution of methylation status of members of the cytochrome P450 family (CYP2R1, CYP27B1, CYP24A1), and Vitamin D Receptor (VDR) genes to vitamin D level variance. CYP2R1 methylation status could regulate the contributing factors affecting the vitamin D serum level and predict response to vitamin D supplementation. Studies revealed that impaired methylation of CYP24A1 occurs in response to an increase in serum level of 25-hydroxyvitamin D (25(OH)D). It is reported that the association between methylation levels of CYP2R1, CYP24A1, and VDR genes and 25(OH)D level is not affected by the methyl-donors bioavailability. CONCLUSIONS: The epigenetic modification of the vitamin D-related genes could explain the vitamin D levels variation among populations. Large-scale clinical trials in various ethnicities are suggested to find the effect of epigenetics on vitamin D response variation. REGISTRATION: The systematic review protocol was registered on PROSPERO (registration number: CRD42022306327).

Effects of DNA methylation on cardiometabolic risk factors: a systematic review and meta-analysis.

BACKGROUND: Epigenetic changes, especially DNA methylation have a main role in regulating cardiometabolic disorders and their risk factors. This study provides a review of the current evidence on the association between methylation of some genes (LINE1, ABCG1, SREBF1, PHOSPHO1, ADRB3, and LEP) and cardiometabolic risk factors. METHODS: A systematic literature search was conducted in electronic databases including Web of Science, PubMed, EMBASE, Google Scholar and Scopus up to end of 2020. All observational human studies (cross-sectional, case-control, and cohort) were included. Studies that assessed the effect of DNA methylation on cardiometabolic risk factors were selected. RESULTS: Among 1398 articles, eight studies and twenty-one studies were included in the meta-analysis and the systematic review, respectively. Our study showed ABCG1 and LINE1 methylation were positively associated with blood pressure (Fisher's zr = 0.07 (0.06, 0.09), 95% CI: 0.05 to 0.08). Methylation in LINE1, ABCG1, SREBF1, PHOSPHO1 and ADRB3 had no significant association with HDL levels (Fisher's zr = - 0.05 (- 0.13, 0.03), 95% CI:-0.12 to 0.02). Positive association was existed between LINE1, ABCG1 and LEP methylation and LDL levels (Fisher's zr = 0.13 (0.04, 0.23), 95% CI: 0.03 to 0.23). Moreover, positive association was found between HbA1C and ABCG1 methylation (Fisher's zr = 0.11 (0.09, 0.13), 95% CI: 0.09 to 0.12). DNA methylation of LINE1, ABCG1 and SREBF1 genes had no significant association with glucose levels (Fisher's zr = 0.01 (- 0.12, 0.14), 95% CI:-0.12 to 0.14). CONCLUSION: This meta-analysis showed that DNA methylation was associated with some cardiometabolic risk factors including LDL-C, HbA1C, and blood pressure. REGISTRATION: Registration ID of the protocol on PROSPERO is CRD42020207677 .

A systematic review and meta-analysis of observational studies on the effects of epigenetic factors on serum triglycerides

ABSTRACT Epigenetic modifications might be associated with serum triglycerides (TG) levels. This study aims to systematically review the studies on the relationship between the methylation of specific cytosine-phosphate-guanine (CpG) sites and serum TG levels. This systematic review and meta-analysis study was conducted according to the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A systematic literature search was conducted in Medline database (PubMed), Scopus, and Cochrane library up to end of 2020. All observational studies (cross-sectional, case-control, and cohort) were included. Studies that assessed the effect of DNA methylation of different CpG sites of ABCG1, CPT1A, and SREBF1 genes on serum TG levels were selected. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. Among 2790 articles, ten studies were included in the quantitative analysis and fourteen studies were included in the systematic review. DNA methylation of ABCG1 gene had significant positive association with TG levels (β = 0.05, 95% CI = 0.04, 0.05, P heterogeneity < 0.001). There was significant inverse association between DNA methylation of CPT1A gene and serum TG levels (β = −0.03, 95% CI = −0.03, −0.02, P heterogeneity < 0.001). DNA methylation of SREBF1 gene was positively and significantly associated with serum TG levels (β = 0.03; 95% CI = 0.02-0.04, P heterogeneity < 0.001). DNA methylation of ABCG1 and SREBF1 genes has positive association with serum TG level, whereas this association is opposite for CPT1A gene. The role of epigenetic factors should be considered in some populations with high prevalence of hypertriglyceridemia.

A systematic review and metaanalysis of observational studies on the effects of epigenetic factors on serum triglycerides.

Epigenetic modifications might be associated with serum triglycerides (TG) levels. This study aims to systematically review the studies on the relationship between the methylation of specific cytosine-phosphate-guanine (CpG) sites and serum TG levels. This systematic review and meta-analysis study was conducted according to the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A systematic literature search was conducted in Medline database (PubMed), Scopus, and Cochrane library up to end of 2020. All observational studies (cross-sectional, case-control, and cohort) were included. Studies that assessed the effect of DNA methylation of different CpG sites of ABCG1, CPT1A, and SREBF1 genes on serum TG levels were selected. The National Institutes of Health (NIH) checklist was used to assess the quality of included articles. Among 2790 articles, ten studies were included in the quantitative analysis and fourteen studies were included in the systematic review. DNA methylation of ABCG1 gene had significant positive association with TG levels (ß = 0.05, 95% CI = 0.04, 0.05, P heterogeneity < 0.001). There was significant inverse association between DNA methylation of CPT1A gene and serum TG levels (ß = -0.03, 95% CI = -0.03, -0.02, P heterogeneity < 0.001). DNA methylation of SREBF1 gene was positively and significantly associated with serum TG levels (ß = 0.03; 95% CI = 0.02-0.04, P heterogeneity < 0.001). DNA methylation of ABCG1 and SREBF1 genes has positive association with serum TG level, whereas this association is opposite for CPT1A gene. The role of epigenetic factors should be considered in some populations with high prevalence of hypertriglyceridemia.

Prenatal and perinatal factors associated with developing multiple sclerosis later in life: A systematic review and meta-analysis.

OBJECTIVE: Both genetic and environmental factors play roles in Multiple Sclerosis (MS) etiopathogenesis. The relationship between prenatal/perinatal factors/exposures and future MS occurrence in the offspring remains controversial. Here, we aimed to review the available evidence on prenatal/perinatal factors associated with later MS occurrence. METHOD: We performed systematic search of PubMed, Web of Science, and Scopus from inception to October 2020. We included original observational studies conducted on human participants addressing the association between prenatal/perinatal factors and MS occurrence. Data were extracted according to the PRISMA guideline. The adjusted odds ratio (OR) with 95% confidence interval (CI) was considered as the desired effect size. The heterogeneity was evaluated by Cochran's Q and I2 and the publication bias was assessed. We excluded gestational/neonatal vitamin D level, season of birth, and latitude because of recently published systematic reviews/meta-analyses on these subjects. RESULTS: Overall, 2306 records were identified in the primary search. After excluding irrelevant studies, we evaluated 34 studies with contributing data on 100 prenatal/perinatal factors associated with an increased or decreased risk of MS occurrence. In the meta-analyses, we found no statistically significant associations between later MS occurrence in offspring and prenatal smoking exposure (OR = 1.01, 95% CI = 0.77-1.34), mode of delivery (OR = 0.90, 95% CI = 0.52-1.56), birth order (OR = 0.85, 95% CI = 0.72-1.00), and maternal age (OR = 1.34, 95% CI = 0.88-2.04). Paternal age and parents' marital status at the time of childbirth, maternal preeclampsia/ toxemia, forceps use, birth weight, plurality, and preterm birth were the other most studied factors, and none reported to affect MS risk. CONCLUSION: We found that prenatal smoking exposure, mode of delivery, birth order, and maternal age do not affect risk of future MS development. Moreover, most of the other investigated factors were reported not to affect MS risk in the offspring.

Intergenerational influence of paternal physical activity on the offspring's brain: A systematic review and meta-analysis.

BACKGROUND: It is well established that parents can influence their offspring's neurodevelopment. It is shown that paternal environment and lifestyle is beneficial for the progeny's fitness and might affect their metabolic mechanisms; however, the effects of paternal exercise on brain in the offspring have not been explored in detail. OBJECTIVE: This study aims to review the impact of paternal physical exercise on memory and learning, neuroplasticity, as well as DNA methylation levels in the offspring's hippocampus. STUDY DESIGN: In this systematic review and meta-analysis, electronic literature search was conducted in databases including PubMed, Scopus, and Web of Science. Eligible studies were those with an experimental design, including an exercise intervention arm, with assessment of any type of memory function, learning ability, or any type of brain plasticity as the outcome measures. Standardized mean difference (SMD) and 95% confidence intervals (CI) were computed as effect size. RESULTS: The systematic review revealed the important role of environmental enrichment in the behavioral development of next generation. Also, offspring of exercised fathers displayed higher levels of memory ability, and lower level of brain-derived neurotrophic factor. A significant effect of paternal exercise on the hippocampal volume was also reported in the few available studies. CONCLUSION: These results suggest an intergenerational effect of paternal physical activity on cognitive benefit, which may be associated with hippocampal epigenetic programming in offspring. However, the biological mechanisms of this modulation remain to be determined.