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

•Polymorphism in DPPIV gene changes the expression under the influence of BCM7 and hydrolyzed milk.•Polymorphism in MOR gene increases expression under the influence of BCM7 and hydrolyzed milk.•The G allele frequency in research population was 0.09 in MOR gene and 0.68 in the DPPIV gene. Autism Spe...

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Published in:	Peptides (New York, N.Y. : 1980) Vol. 65; pp. 6 - 11
Main Authors:	Cieślińska, Anna, Sienkiewicz-Szłapka, Edyta, Wasilewska, Jolanta, Fiedorowicz, Ewa, Chwała, Barbara, Moszyńska-Dumara, Małgorzata, Cieśliński, Tomasz, Bukało, Marta, Kostyra, Elżbieta
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2015
Subjects:	Adolescent Alleles Animals ASD Autism Autistic Disorder - genetics Autistic Disorder - metabolism Autistic Disorder - physiopathology Case-Control Studies Cattle Child Child, Preschool Dipeptidyl Peptidase 4 - genetics Dipeptidyl Peptidase 4 - metabolism Dipeptidyl peptidase IV Endorphins - administration & dosage Endorphins - metabolism Female Gene Expression Regulation Gene Frequency Gene polymorphism Genotype Humans Male Milk Proteins - chemistry Peptide Fragments - administration & dosage Peptide Fragments - metabolism Poland Polymorphism, Single Nucleotide Protein Hydrolysates - administration & dosage Protein Hydrolysates - metabolism Receptors, Opioid, mu - genetics Receptors, Opioid, mu - metabolism Young Adult β-Casomorphin-7 μ-Opioid receptor Poland μ-Opioid receptor Autism ASD Dipeptidyl peptidase IV β-Casomorphin-7 Gene polymorphism
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Summary:	•Polymorphism in DPPIV gene changes the expression under the influence of BCM7 and hydrolyzed milk.•Polymorphism in MOR gene increases expression under the influence of BCM7 and hydrolyzed milk.•The G allele frequency in research population was 0.09 in MOR gene and 0.68 in the DPPIV gene. 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 3.4.14.5) 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0196-9781 1873-5169
DOI:	10.1016/j.peptides.2014.11.012