Stress-related genetic components in attention-deficit/hyperactivity disorder (ADHD): Effects of the SERPINA6 and SERPINA1 genetic markers in a family-based brazilian sample

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dc.contributor.authorCarpena M.X.
dc.contributor.authorSanchez-Luquez K.Y.
dc.contributor.authorMartins-Silva T.
dc.contributor.authorSantos T.M.
dc.contributor.authorFarias C.P.
dc.contributor.authorLeventhal D.G.P.
dc.contributor.authorBerruti B.
dc.contributor.authorZeni C.P.
dc.contributor.authorSchmitz M.
dc.contributor.authorChazan R.
dc.contributor.authorHutz M.H.
dc.contributor.authorSalatino-Oliveira A.
dc.contributor.authorGenro J.P.
dc.contributor.authorRohde L.A.
dc.contributor.authorTovo-Rodrigues L.
dc.date.accessioned2024-03-12T19:15:10Z
dc.date.available2024-03-12T19:15:10Z
dc.date.issued2022
dc.description.abstract© 2022 Elsevier LtdSERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus–Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying this relationship are still unclear. Evaluation of the SERPINA6/SERPINA1 gene cluster in ADHD may provide relevant information to uncover them. We tested the association between the SERPINA6/SERPINA1 locus, including 95 single nucleotide polymorphisms (SNPs), and ADHD, using data from a Brazilian clinical sample of 259 ADHD probands and their parents. The single SNP association was tested using binary logistic regression, and we performed Classification and Regression Tree (CART) analysis to evaluate genotype combinations' effects on ADHD susceptibility. We assessed SNPs’ regulatory effects through the Genotype-Tissue Expression (GTEx) v8 tool, and performed a complementary look-up analysis in the largest ADHD GWAS to date. There was a suggestive association between ADHD and eight variants located in the SERPINA6 region and one in the intergenic region between SERPINA6 and SERPINA1 after correction for multiple tests (p < 0.032). CART analysis showed that the combined effects of genotype GG in rs2144833 and CC in rs10129500 were associated with ADHD (OR = 1.78; CI95% = 1.24–2.55). The GTEx assigned the SNPs as eQTLs for genes in different tissues, including SERPINA6, and the look-up analysis revealed two SNPs associated with ADHD. These results suggest a shared genetic component between cortisol levels and ADHD. HPA dysregulation/altered stress response in ADHD might be mediated by upregulation of corticosteroid binding globulin (CBG, encoded by SERPINA6) expression.
dc.description.firstpage1
dc.description.lastpage9
dc.description.volume149
dc.identifier.doi10.1016/j.jpsychires.2022.02.014
dc.identifier.issn1879-1379
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/34373
dc.relation.ispartofJournal of Psychiatric Research
dc.rightsAcesso Restrito
dc.subject.otherlanguageADHD
dc.subject.otherlanguageCortisol
dc.subject.otherlanguageGWAS
dc.subject.otherlanguageHPA axis Dysregulation
dc.subject.otherlanguageSERPINA6
dc.titleStress-related genetic components in attention-deficit/hyperactivity disorder (ADHD): Effects of the SERPINA6 and SERPINA1 genetic markers in a family-based brazilian sample
dc.typeArtigo
local.scopus.citations4
local.scopus.eid2-s2.0-85125993934
local.scopus.subjectalpha 1-Antitrypsin
local.scopus.subjectAttention Deficit Disorder with Hyperactivity
local.scopus.subjectBrazil
local.scopus.subjectGenetic Markers
local.scopus.subjectGenotype
local.scopus.subjectHumans
local.scopus.subjectHydrocortisone
local.scopus.subjectPolymorphism, Single Nucleotide
local.scopus.subjectTranscortin
local.scopus.updated2024-12-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85125993934&origin=inward
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