HLA-G∗14bp Insertion and the KIR2DS1-HLAC2 Complex Impact on Behavioral Impairment in Children with Autism Spectrum Disorders

Neuroscience. 2018 Feb 1:370:163-169. doi: 10.1016/j.neuroscience.2017.06.012. Epub 2017 Jun 13.

Abstract

Activating KIR-HLA-C ligand complexes and HLA-G∗14bp insertion/deletion (+/-) polymorphism were associated to Autism Spectrum Disorders (ASD) and were suggested to correlate with inflammation during fetal development. We evaluated whether HLA-G∗14bp(+/-) and KIR-HLA-C complexes are associated with cognitive and behavioral scores and EEG profile in 119 ASD children (58 from Sardinia, 61 from Peninsular Italy). KIR2DS1-C2; KIR2DS2-C1; KIR2DL1-C2; KIR2DL2-C1; KIR2DL3-C1 and HLA-G∗14bp(+/-) were molecularly genotyped by Single Specific Primer PCR and gel electrophoresis. Univariate linear model analysis adjusted for age, gender and provenience showed statistically higher scores of Childhood Autism Rating Scale (CARS) and Autistic Core Behavior in KIR2DS1-C2+/HLA-G∗14bp+ASD children (43.7±1.5, p=0.03; 3.3±0.1, p=0.03, respectively). These results suggested a synergistic polygenic association of KIR2DS1-HLAC2+/HLA-G∗14bp+ pattern with behavioral impairment in ASD children.

Keywords: Autism Spectrum Disorders; HLA-C; HLA-G14; KIR 2DS1; behavior; in utero immunology.

MeSH terms

  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology
  • Autism Spectrum Disorder / psychology*
  • Brain / physiopathology
  • Child
  • Cohort Studies
  • Electroencephalography
  • Female
  • HLA-C Antigens / genetics*
  • HLA-G Antigens / genetics*
  • Humans
  • INDEL Mutation*
  • Male
  • Multifactorial Inheritance
  • Psychiatric Status Rating Scales
  • Receptors, KIR / genetics*
  • White People / genetics

Substances

  • HLA-C Antigens
  • HLA-G Antigens
  • KIR2DS1 protein, human
  • Receptors, KIR