HLA-G allelic distribution in Sardinian children with Autism spectrum disorders: A replication study

Recent results show that in mainland Italian children with Autism spectrum disorder (ASD), HLA-G coding
alleles distribution is skewed and an association between HLA-G*01:05N and ASD is present.
Herein, in an independent cohort of Sardinian ASD (sASD) children and their relatives, we verify whether
HLA-G allele association with ASD could be confirmed in this genetically peculiar insular population.
One hundred children with a diagnosis of ASD, born in Sardinia and of Sardinian descent, 91 of their mothers,
and 40 of their healthy siblings were enrolled. DNA sequencing analysis of HLA-G exon 2, 3 and 4 was used to
obtain HLA-G allelic frequencies. Alleles distribution was compared with that of continental ASD children and
with a control group of Caucasoid couples of multiparous women and their partners from Brazil and Denmark.
Skewing of HLA-G allele distribution was replicated in sASD children; in particular, the HLA-G*01:03 allele,
associated with reduced fetal tolerogenicity and development of myeloid leukemia, was more common in both
ASD groups compared to controls (pc = 1 × 10−3
; OR:3.5, 95%CI: 1.8–6.8). However, given the lack of data on
HLA-G*01:03 allelic distribution among Sardinian healthy subjects, we cannot exclude a population effect.
These data confirm an association of HLA-G locus with ASD development, particularly with those alleles
linked to a lower expression of tolerogenic HLA-G protein, thus warranting further studies on HLA-G polymorphism distribution in different ASD populations