Food and Behaviour Research

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Influence of candidate polymorphisms on the dipeptidyl peptidase IV and μ-opioid receptor genes expression in aspect of the β-casomorphin-7 modulation functions in autism.

Cieslinska A, Sienkiewicz-Szlapka E, Wasilewska J, Fiedorowicz E, Chwala B, Moszynriska-Dumara M, Cieslinski T, Bukalo M, Kostyra E (2015) Peptides.   doi: 10.1016/j.peptides.2014.11.012. [Epub ahead of print] Elsevier Inc

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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with population prevalence of approximately 60-70 per 10,000. Data shows that both opioid system function enhancement and opiate administration can result in autistic-like symptoms.

Cow milk opioid peptides, including β-casomorphin-7 (BCM7, Tyr-Pro-Phe-Pro-Gly-Pro-Ile), affect the μ-opioid receptor (MOR) and are subjected to degradation resulting from the proline
dipeptidyl peptidase IV (DPPIV, EC enzyme activity.

The presence of MOR and DPPIV activity are crucial factors determining biological activity of BCM7 in the human body.

Our study examined the effect of β-casomorphin-7 on the MOR and DPPIV genes expression according to specific point mutations in these genes.

In addition, we investigated frequency of A118G SNP in the MOR gene and rs7608798 of the DPPIV (A/G) gene in healthy and autistic children.

Our research indicated correlation in DPPIV gene expression under the 
influence of BCM7 and hydrolyzed milk between healthy and ASD-affected children with genotype GG (P<0.0001).

We also observed increased MOR gene expression in healthy children with genotype AG at polymorphic site A118G under 
influence of BCM7 and hydrolyzed milk.  The G allele frequency was 0.09 in MOR gene and 0.68 in the DPPIV gene.

But our results suggest no association between presence of the alleles G and A at position rs7608798 in DPPIV gene nor alleles A and G at position A118G of the MOR and increased incidence of ASD.

Our studies emphasize the compulsion for genetic analysis in correlation with genetic factors affecting development and enhancement of autism symptoms.


Sensitivity to opioid peptides derived from food, including BCM-7 (from cows' milk) and gliadomorphin (from gluten grains) has long been suspected as playing a role in some symptoms of Autistic Spectrum Disorders and related developmental and mental health conditions, including ADHD and the schizophrenia spectrum, among others.

A major problem in both research and clinical practice is the huge individual variability within any group defined by these purely descriptive labels, which are based entirely on observed or reported behaviour.  For better targeting and development of effective methods of management (either medications or dietary interventions), useful biomarkers are therefore needed, but remain lacking.

In this study, researchers investigated the effects of beta-casomorphin-7 (BCM-7) - an opioid peptide derived from the digestion of standard cows' milk - on the expression of two genes known to be critical in determining the effects of BCM-7 at the individual level:

(1) the mu-opioid receptor (MOR) - activity of which determines sensitivity to the opioid effects of BCM-7.
(2) the gene for DPP-IV - an enzyme needed to break down, and so inactivate, BCM-7.

Differential effects of BCM-7 according to genotype were found for the expression of both of these genes (in children with ASD and also in controls). 

The frequency of different gene variants was also reported, and although no clear associations were found between this and ASD status in this pilot study, the researchers emphasise the need for future research to take into account individual genetic variation.

See also:

And for more information on potential effects of BCM-7 (derived from A1, rather than A2 milk proteins), see: