Polymorphism of interleukin-1β and interleukin-1 receptor antagonist genes in children with autism spectrum disorders

Khaled Saad; Alam-Eldin M Abdallah; Ahmed A Abdel-Rahman; Abdulrahman A Al-Atram; Yasser F Abdel-Raheem; Eman Fathallah Gad; Mohamed Gamil M Abo-Elela; Yasser M Elserogy; Amira Elhoufey; Dalia A Nigm; Eman M Nagiub Abdelsalam; Thamer A M Alruwaili

doi:10.1016/j.pnpbp.2020.109999

Polymorphism of interleukin-1β and interleukin-1 receptor antagonist genes in children with autism spectrum disorders

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20:103:109999. doi: 10.1016/j.pnpbp.2020.109999. Epub 2020 Jun 9.

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt. Electronic address: khaled.ali@med.au.edu.eg.
² Department of Pediatrics, Faculty of Medicine, Assiut University, Assiut, Egypt.
³ Department of Neuropsychiatry, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁴ Department of Psychiatry, College of Medicine, Majmaah University, Majmaah, Saudi Arabia.
⁵ Department of Community Health Nursing, Faculty of Nursing, Assiut University, Egypt; Department of Community Health Nursing, Alddrab University College, Jazan University, Saudi Arabia.
⁶ Clinical Pathology Department, Faculty of Medicine, Assiut University, Egypt.
⁷ Department of Pediatrics, Faculty of Medicine, Aljouf University, Saudi Arabia.

PMID: 32526258
DOI: 10.1016/j.pnpbp.2020.109999

Abstract

In this study, we first investigated interleukin-1 beta (IL-1β) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions -31 and - 511 of the IL-1β gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1β promoter polymorphism at -511 (IL-1β-511) and - 31 (IL-1β-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1β and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1β-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1β-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1β-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1β system, with abnormally increased serum levels of IL-1β and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1β-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1β-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1β and IL-1RA systems may have a role in the pathophysiology of ASD.

Keywords: Autism; Children; Interleukin-1 beta; Polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Autism Spectrum Disorder / genetics*
Autism Spectrum Disorder / psychology
Case-Control Studies
Child
Child, Preschool
DNA / genetics
Female
Genotype
Humans
Interleukin 1 Receptor Antagonist Protein / genetics*
Interleukin-1beta / blood
Interleukin-1beta / genetics*
Male
Polymorphism, Genetic
Polymorphism, Single Nucleotide / genetics
Promoter Regions, Genetic

Substances

IL1B protein, human
IL1RN protein, human
Interleukin 1 Receptor Antagonist Protein
Interleukin-1beta
DNA