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Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?

INTRODUCTION: In 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 in...

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Autores principales: Bennabi, Meriem, Delorme, Richard, Oliveira, José, Fortier, Catherine, Lajnef, Mohamed, Boukouaci, Wahid, Feugeas, Jean-Paul, Marzais, François, Gaman, Alexandru, Charron, Dominique, Ghaleh, Bijan, Krishnamoorthy, Rajagopal, Leboyer, Marion, Tamouza, Ryad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564239/
https://www.ncbi.nlm.nih.gov/pubmed/26352598
http://dx.doi.org/10.1371/journal.pone.0137339
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author Bennabi, Meriem
Delorme, Richard
Oliveira, José
Fortier, Catherine
Lajnef, Mohamed
Boukouaci, Wahid
Feugeas, Jean-Paul
Marzais, François
Gaman, Alexandru
Charron, Dominique
Ghaleh, Bijan
Krishnamoorthy, Rajagopal
Leboyer, Marion
Tamouza, Ryad
author_facet Bennabi, Meriem
Delorme, Richard
Oliveira, José
Fortier, Catherine
Lajnef, Mohamed
Boukouaci, Wahid
Feugeas, Jean-Paul
Marzais, François
Gaman, Alexandru
Charron, Dominique
Ghaleh, Bijan
Krishnamoorthy, Rajagopal
Leboyer, Marion
Tamouza, Ryad
author_sort Bennabi, Meriem
collection PubMed
description INTRODUCTION: In 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 METHODS: 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). 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. RESULTS: We 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). CONCLUSION: Our 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.
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spelling pubmed-45642392015-09-17 Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders? Bennabi, Meriem Delorme, Richard Oliveira, José Fortier, Catherine Lajnef, Mohamed Boukouaci, Wahid Feugeas, Jean-Paul Marzais, François Gaman, Alexandru Charron, Dominique Ghaleh, Bijan Krishnamoorthy, Rajagopal Leboyer, Marion Tamouza, Ryad PLoS One Research Article INTRODUCTION: In 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 METHODS: 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). 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. RESULTS: We 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). CONCLUSION: Our 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. Public Library of Science 2015-09-09 /pmc/articles/PMC4564239/ /pubmed/26352598 http://dx.doi.org/10.1371/journal.pone.0137339 Text en © 2015 Bennabi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bennabi, Meriem
Delorme, Richard
Oliveira, José
Fortier, Catherine
Lajnef, Mohamed
Boukouaci, Wahid
Feugeas, Jean-Paul
Marzais, François
Gaman, Alexandru
Charron, Dominique
Ghaleh, Bijan
Krishnamoorthy, Rajagopal
Leboyer, Marion
Tamouza, Ryad
Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title_full Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title_fullStr Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title_full_unstemmed Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title_short Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders?
title_sort dectin-1 polymorphism: a genetic disease specifier in autism spectrum disorders?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564239/
https://www.ncbi.nlm.nih.gov/pubmed/26352598
http://dx.doi.org/10.1371/journal.pone.0137339
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