title: 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.
abstract: 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.
authors.affiliation: Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-19 Olsztyn, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Cieślińska
authors.affiliation: Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-19 Olsztyn, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Sienkiewicz-Szłapka
authors.affiliation: Department of Paediatrics, Gastroenterology and Allergology, Medical University of Białystok, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Wasilewska
authors.affiliation: Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-19 Olsztyn, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Fiedorowicz
authors.affiliation: Regional Children's Hospital in Olsztyn, Zolnierska 18 A Street, 10-561 Olsztyn, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Chwała
authors.affiliation: Center for Diagnosis, Treatment and Therapy of Autism at the Regional Children's Hospital in Olsztyn, Zolnierska 18 A Street, 10-561 Olsztyn, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Moszyńska-Dumara
authors.affiliation: Center for Diagnosis, Treatment and Therapy of Autism at the Regional Children's Hospital in Olsztyn, Zolnierska 18 A Street, 10-561 Olsztyn, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cieśliński
authors.affiliation: Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-19 Olsztyn, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Bukało
authors.affiliation: Faculty of Biology and Biotechnology, University of Warmia and Mazury, Oczapowskiego 1A Street, 10-19 Olsztyn, Poland. Electronic address: elzbieta.kostyra@uwm.edu.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kostyra
mesh_terms: D000293:Adolescent; D000483:Alleles; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism; D004723:Endorphins / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008894:Milk Proteins / Q000737:chemistry; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011492:Protein Hydrolysates / Q000008:administration & dosage* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004723:Endorphins; D008894:Milk Proteins; C485764:OPRM1 protein, human; D010446:Peptide Fragments; D011492:Protein Hydrolysates; D017450:Receptors, Opioid, mu; C041128:beta-casomorphin 7; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: ASD; Autism; Dipeptidyl peptidase IV; Gene polymorphism; β-Casomorphin-7; μ-Opioid receptor