DNA Methylation Analysis of HTR2A Regulatory Region in Leukocytes of Autistic Subjects.
Autistic adults who carry the AG form of rs6311 show extra methylation on the serotonin 2A receptor gene, hinting at dampened serotonin signaling.
01Research in Context
What this study did
Scientists drew blood from autistic adults and from matched controls.
They checked who carried the AG form of gene variant rs6311.
Then they measured how tightly the HTR2A promoter was tagged with methyl groups.
What they found
Autistic adults with the AG genotype had more methylation on the serotonin 2A receptor gene.
More methylation usually means less gene activity, so serotonin signaling may be dampened in these individuals.
How this fits with other research
Noroozi et al. (2016) used the same case-control design and also linked a single gene variant to autism risk, but they looked at the glutamate GRM7 gene instead of the serotonin HTR2A gene.
Together the two 2016 studies point to both glutamate and serotonin genes in autism biology.
Soghomonian et al. (2017) took a different route and measured parvalbumin mRNA directly in post-mortem brain tissue, finding lower levels in autistic cerebellum.
That brain study seems to clash because it shows less gene expression, while Dubravka finds more methylation (which should also lower expression).
The difference is tissue: leukocytes versus brain. Methylation in blood may not mirror methylation in neurons, so both findings can be true at the same time.
Why it matters
You cannot scan a client’s brain in clinic, but a simple blood test might flag altered serotonin biology in adults with the AG genotype. If you see unusual responses to serotonergic medications, remember this epigenetic clue and consider coordinating with medical providers for dose or drug adjustments.
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02At a glance
03Original abstract
Disturbed brain and peripheral serotonin homeostasis is often found in subjects with autism spectrum disorder (ASD). The role of the serotonin receptor 2A (HTR2A) in the regulation of central and peripheral serotonin homeostasis, as well as its altered expression in autistic subjects, have implicated the HTR2A gene as a major candidate for the serotonin disturbance seen in autism. Several studies, yielding so far inconclusive results, have attempted to associate autism with a functional SNP -1438 G/A (rs6311) in the HTR2A promoter region, while possible contribution of epigenetic mechanisms, such as DNA methylation, to HTR2A dysregulation in autism has not yet been investigated. In this study, we compared the mean DNA methylation within the regulatory region of the HTR2A gene between autistic and control subjects. DNA methylation was analysed in peripheral blood leukocytes using bisulfite conversion and sequencing of the HTR2A region containing rs6311 polymorphism. Autistic subjects of rs6311 AG genotype displayed higher mean methylation levels within the analysed region than the corresponding controls (P < 0.05), while there was no statistically significant difference for AA and GG carriers. Our study provides preliminary evidence for increased HTR2A promoter methylation in leukocytes of a portion of adult autistic subjects, indicating that epigenetic mechanisms might contribute to HTR2A dysregulation observed in individuals with ASD.
Autism research : official journal of the International Society for Autism Research, 2016 · doi:10.1002/aur.1519