APOE hypermethylation is associated with autism spectrum disorder in a Chinese population

Abstract

Abnormal apolipoprotein E (APOE) methylation has been demonstrated to be associated with Alzheimer's disease, which may have overlapping mechanisms with autism spectrum disorder (ASD). Thus, the purpose of the present study was to assess the possible link between APOE methylation and ASD. Genomic DNA was extracted from peripheral blood and subjected to a methylation assay. SYBR green-based quantitative methylation-specific polymerase chain reaction analysis was used to measure APOE methylation in 62 pediatric patients with ASD and 73 age-matched healthy subjects. The APOE methylation in each sample was expressed as a percentage of methylation of a reference (PMR). The results indicated that APOE methylation in pediatric patients with ASD was significantly higher than that in the healthy controls (median PMR, 33 vs. 11%; P=2.36×10−10). Receiver operating characteristic curve demonstrated that PMR of 15.4% was the optimal cut-off for predicting ASD (area under curve, 0.817; sensitivity, 93.5%; specificity, 72.6%; P=2.36×10−10). In summary, the present results indicated that APOE hypermethylation in peripheral blood DNA may be used as a diagnostic biomarker for ASD.

Integrative Analysis of shared Genetic Pathogenesis by Autism Spectrum Disorder and Obsessive-Compulsive Disorder

“…For the 2017-based analysis, results revealed 6 OCD genes also present significant differences (FDR corrected p-value<0.05) between ASD cases and healthy controls, including 2 genes (TSPO and APOE) from GSE28521 and 5 genes (CDH2, ADCY8, APOE, TOR1A, and OLIG2) from GSE38322. Notably, the gene APOE that has been identified in both datasets in the 2017based analysis were reported to have a potential association with ASD in a recent study [15], with supported the effectiveness of the proposed workflow. It has been shown that APOE methylation in pediatric patients with ASD was significantly higher than that in the healthy controls (median PMR, 33 vs. 11%; P=2.36×10−10).…”

“…3a), and seven genes (CDH2, ADCY8, APOE, TOR1A, OLIG2, DISP1, and SETD1A) from GSE38322 passed the FDR. To note, two genes (DISP1 and SETD1A) were newly identified in the 2019-based analysis, and the gene APOE were replicated by a recently published study [15], which showed that APOE presented a significant association with ASD in a DNA methylation analysis. The replication 5 demonstrated the effectiveness of the workflow proposed in this study.…”

Integrative analysis of shared genetic pathogenesis by autism spectrum disorder and obsessive-compulsive disorder

“…Figure 3 showed that two genes ( TSPO and APOE ) from GSE28521 passed the P =0.05 FDR (Figure 3A), and seven genes ( CDH2, ADCY8, APOE, TOR1A, OLIG2, DISP1 , and SETD1A ) from GSE38322 passed the FDR. To note, two genes ( DISP1 and SETD1A ) were newly identified in the 2019-based analysis, and the gene APOE was replicated by a recently published study [15], which showed that APOE presented a significant association with ASD in DNA methylation analysis. The replication demonstrated the effectiveness of the workflow proposed in the present study.…”

Genes involved in cholesterol cascades are linked to brain connectivity in one third of autistic patients

“…Hence, the entries of indicate the number of partitions in which subjects and are assigned to the same group, divided by the number of partitions. Eventually, the consensus matrix is averaged over the range in the interval (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), so that information about the underlying structure at different resolutions is combined in the final consensus matrix, for more details see (35).…”

“…However, the factors driving this disease are not well understood, making therapeutic interventions to restore the E/I balance in ASD a major challenge (12). Motivated by the Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition with ASD symptoms characterized by impaired cholesterol biosynthesis (13), factors related to the synthesis, metabolism and transport of lipids, cholesterol and other lipoproteins might plays a relatively general role in ASD (14)(15)(16). Indeed, a therapeutic intervention based on cholesterol supplements has been attempted (17), although the final results of these studies and the therapeutic benefits at the behavioural level are not yet clear.…”