Abstract
IntroductionIn autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro-intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin-1.Material and methodsDNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann–Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis.ResultsWe found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01).ConclusionOur data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype.
Highlights
In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress
We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in healthy controls (HC) as compared to ASD but failed to reach statistical significance for the latter
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interactions and communication with a restricted repertoire of interests, behavior and activities [1]
Summary
DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). This study was conducted in a sample of subjects with ASD enrolled in the PARIS (Paris Autism Research International Sibpair) cohort in specialized clinical neuropsychiatric centers established in France and in Sweden [33]. Diagnosis was based on comprehensive clinical evaluation by expert clinicians using DSM IV-TR criteria. Cases were included only after a thorough clinical evaluation, including psychiatric and neuropsychological examination, standard karyotyping, and fragileX testing, as well as brain imaging and EEG as required. The healthy control (HC) group consists of clinically assessed unrelated healthy individuals, both enrolled under the previously published selective criteria [34, 35]. All controls and most of the individuals included were of European descent
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