Abstract
Original language | English |
---|---|
Article number | 7758 |
Number of pages | 11 |
Journal | Sci. Rep. |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2020 |
Keywords
- haptoglobin
- allele
- autism
- case control study
- child
- female
- genetics
- haplotype
- human
- male
- preschool child
- single nucleotide polymorphism
- Alleles
- Autism Spectrum Disorder
- Case-Control Studies
- Child
- Child, Preschool
- Female
- Haplotypes
- Haptoglobins
- Humans
- Male
- Polymorphism, Single Nucleotide
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Assessment of haptoglobin alleles in autism spectrum disorders : Scientific Reports. / Cupaioli, F.A.; Mosca, E.; Magri, C.; Gennarelli, M.; Moscatelli, M.; Raggi, M.E.; Landini, M.; Galluccio, N.; Villa, L.; Bonfanti, A.; Renieri, A.; Fallerini, C.; Minelli, A.; Marabotti, A.; Milanesi, L.; Fasano, A.; Mezzelani, A.
In: Sci. Rep., Vol. 10, No. 1, 7758, 2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Assessment of haptoglobin alleles in autism spectrum disorders
T2 - Scientific Reports
AU - Cupaioli, F.A.
AU - Mosca, E.
AU - Magri, C.
AU - Gennarelli, M.
AU - Moscatelli, M.
AU - Raggi, M.E.
AU - Landini, M.
AU - Galluccio, N.
AU - Villa, L.
AU - Bonfanti, A.
AU - Renieri, A.
AU - Fallerini, C.
AU - Minelli, A.
AU - Marabotti, A.
AU - Milanesi, L.
AU - Fasano, A.
AU - Mezzelani, A.
N1 - Cited By :1 Export Date: 10 February 2021 Correspondence Address: Mezzelani, A.; Institute of Biomedical Technologies, Via Fratelli Cervi 93, Italy; email: alessandra.mezzelani@itb.cnr.it Chemicals/CAS: haptoglobin, 9087-69-8; Haptoglobins Funding details: Horizon 2020, 825033, GTB18001 Funding details: GR-2009-1570296 Funding details: PB05 Funding text 1: Grants received in support of research work: Italian Ministry of Health (GR-2009-1570296); Italian Flagship-project InterOmics (PB05); European Union’s Horizon 2020 GEMMA project (grant agreement No 825033), www.gemma-project.eu. The Cell line and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases, member of the Telethon Network of Genetic Biobanks (project no. GTB18001), funded by Telethon Italy, and of the EuroBioBank network, provided us with specimens. We thank John Hatton of the Institute of Biomedical Technologies (CNR-ITB) for proofreading the manuscript. Funding text 2: F.A.C. participated in wet and statistical analysis, wrote the paper; E.M. bioinformatics analyses; M.G., C.M. generated SNP-array genotypes of the Brescia cohort; M.M. bioinformatics infrastructure development; M.L., N.G. wet analyses; A.B. patients recruitment; L.V. and M.M. ASD diagnosis; M.E.R. recruitment coordination; A.R. and F.C. provided DNA and diagnosis of Telethon patients; A. Mi. evaluation and recruitment of “super controls”; A.Ma. P.I. of the project funded by Italian Ministry of Health; L.M. responsible of the Italian Flagship-project InterOmics (PB05), A.Me. conceived and designed the study, participated in wet and statistical analysis, wrote the paper. F.A. data interpretation and final revision. All the authors critically revised the manuscript. 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PY - 2020
Y1 - 2020
N2 - Gene-environment interactions, by means of abnormal macromolecular intestinal adsorption, is one of the possible causes of autism spectrum disorders (ASD) predominantly in patients with gastrointestinal disorders. Pre-haptoglobin-2 (zonulin), encoded by the Haptoglobin (HP) allele-2 gene, enhances the intestinal permeability by modulation of intercellular tight junctions. The two alleles of HP, HP1 and HP2, differ for 2 extra exons in HP2 that result in exon duplication undetectable by classic genome-wide association studies. To evaluate the role of HP2 in ASD pathogenesis and to set up a method to discriminate HP alleles, Italian subjects with ASD (n = 398) and healthy controls (n = 379) were genotyped by PCR analysis; subsequently, the PCR results were integrated with microarray genotypes (Illumina Human Omni 1S-8), obtained using a subset from the same subjects, and then we developed a computational method to predict HP alleles. On the contrary to our expectations, there was no association between HP2 and ASD (P > 0.05), and there was no significant allele association in subjects with ASD with or without gastrointestinal disorders (P > 0.05). With the aid of bioinformatics analysis, from a window frame of ~2 Mb containing 314 SNPs, we obtain imputation accuracy (r2) between 0.4 and 0.9 (median 0.7) and correct predictions were between 70% and 100% (median 90%). The conclusions endorse that enhanced intestinal permeability in subjects with ASD should not be imputed to HP2 but to other members of the zonulin family and/or to environmental factors. © 2020, The Author(s).
AB - Gene-environment interactions, by means of abnormal macromolecular intestinal adsorption, is one of the possible causes of autism spectrum disorders (ASD) predominantly in patients with gastrointestinal disorders. Pre-haptoglobin-2 (zonulin), encoded by the Haptoglobin (HP) allele-2 gene, enhances the intestinal permeability by modulation of intercellular tight junctions. The two alleles of HP, HP1 and HP2, differ for 2 extra exons in HP2 that result in exon duplication undetectable by classic genome-wide association studies. To evaluate the role of HP2 in ASD pathogenesis and to set up a method to discriminate HP alleles, Italian subjects with ASD (n = 398) and healthy controls (n = 379) were genotyped by PCR analysis; subsequently, the PCR results were integrated with microarray genotypes (Illumina Human Omni 1S-8), obtained using a subset from the same subjects, and then we developed a computational method to predict HP alleles. On the contrary to our expectations, there was no association between HP2 and ASD (P > 0.05), and there was no significant allele association in subjects with ASD with or without gastrointestinal disorders (P > 0.05). With the aid of bioinformatics analysis, from a window frame of ~2 Mb containing 314 SNPs, we obtain imputation accuracy (r2) between 0.4 and 0.9 (median 0.7) and correct predictions were between 70% and 100% (median 90%). The conclusions endorse that enhanced intestinal permeability in subjects with ASD should not be imputed to HP2 but to other members of the zonulin family and/or to environmental factors. © 2020, The Author(s).
KW - haptoglobin
KW - allele
KW - autism
KW - case control study
KW - child
KW - female
KW - genetics
KW - haplotype
KW - human
KW - male
KW - preschool child
KW - single nucleotide polymorphism
KW - Alleles
KW - Autism Spectrum Disorder
KW - Case-Control Studies
KW - Child
KW - Child, Preschool
KW - Female
KW - Haplotypes
KW - Haptoglobins
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
U2 - 10.1038/s41598-020-64679-w
DO - 10.1038/s41598-020-64679-w
M3 - Article
VL - 10
JO - Sci. Rep.
JF - Sci. Rep.
SN - 2045-2322
IS - 1
M1 - 7758
ER -