Showing posts with label DLGAP2. Show all posts
Showing posts with label DLGAP2. Show all posts

Thursday 5 September 2019

Cannabis Use and Potential Epigenetic Damage to Autism Genes

Today we consider another risk factor that may be contributing to the increase in prevalence of autism and it is about the father, for a change.  In the public's perception cannabis is a safe alternative way to treat all kinds of medical problems, many experts do not agree.

Fathers who use marijuana may be using it for two, suggests a study from Duke Medical Center. Although the study is small, encompassing just 24 men and 15 rats, it highlights a potential transgenerational effect of marijuana exposure—the passing on of sperm in which an autism-associated gene, DLGAP2, has accumulated extra epigenetic marks.
The Duke scientists, led by Susan Murphy, PhD, associate professor of obstetrics and gynecology, identified significant hypomethylation at DLGAP2 in the sperm of men who used marijuana compared to controls. A similar observation was made in the sperm of rats exposed to tetrahydrocannabinol (THC) compared to controls. This hypomethylated state was also detected in the forebrain region of rats born to fathers exposed to THC.
Murphy and colleagues said their findings do not establish a definitive link between cannabis use and autism, but the possible connection warrants further, urgent study, given efforts throughout the country to legalize marijuana for recreational and/or medicinal uses.
This study is the first to demonstrate an association between a man’s cannabis use and changes of a gene in sperm that has been implicated in autism,” she emphasized. “Given marijuana’s increasing prevalence of use in the United States and the increasing numbers of states that have legalized its use, we need more studies to understand how this drug is affecting not only those who smoke it, but their unborn children.
“There’s a perception that marijuana is benign. More studies are needed to determine whether that is true.”
The original paper:-

Parental cannabis use has been associated with adverse neurodevelopmental outcomes in offspring, but how such phenotypes are transmitted is largely unknown. Using reduced representation bisulphite sequencing (RRBS), we recently demonstrated that cannabis use is associated with widespread DNA methylation changes in human and rat sperm. Discs-Large Associated Protein 2 (DLGAP2), involved in synapse organization, neuronal signaling, and strongly implicated in autism, exhibited significant hypomethylation (p < 0.05) at 17 CpG sites in human sperm. We successfully validated the differential methylation present in DLGAP2 for nine CpG sites located in intron seven (p < 0.05) using quantitative bisulphite pyrosequencing. Intron 7 DNA methylation and DLGAP2 expression in human conceptal brain tissue were inversely correlated (p < 0.01). Adult male rats exposed to delta-9-tetrahydrocannabinol (THC) showed differential DNA methylation at Dlgap2 in sperm (p < 0.03), as did the nucleus accumbens of rats whose fathers were exposed to THC prior to conception (p < 0.05). Altogether, these results warrant further investigation into the effects of preconception cannabis use in males and the potential effects on subsequent generations.


I do not think anyone should be surprised that the THC in cannabis may leave an epigenetic tag on the DNA of the user and that it is passed down to following generations. We saw a long time ago that the same applies to people who smoke. It is just a question of which genes are most affected.  In the case of smoking it affected how your body deals with oxidative stress and this blocked how drugs for severe asthma (COPD) should work, so making COPD a very big problem for ex-smokers. Stopping smoking does not make the problem go away.

Any kind of prolonged chemical exposure may be a problem, the lead that was used in gasoline/petrol, current use of potent pesticides etc.  The same applies to electrical/magnetic exposure. Best not to live very close to high voltage power lines, or have a mobile phone mast on top of your building.

The concern is that these epigenetic markers are heritable and so accumulate over the generations, a kind of epigenetic pollution.

If great great grandpa worked down a coal mine or in a chemical factory, it may be recorded in your DNA.