Cited by 14Schizophrenia research and treatmentGenetic Associations and EpidemiologyProtease and Inhibitor Mechanisms

Genetic variations in the ADAMTS12 gene are associated with schizophrenia in Puerto Rican patients of Spanish descent

Bespalova, Irina N., Angelo, Gary W., Ritter, Ben P., Hunter, Jason, Reyes-Rabanillo, Maria L., Siever, Larry J., Silverman, Jeremy M.·2012·NeuroMolecular Medicine

Abstract

ADAMTS12 belongs to the family of metalloproteinases that mediate a communication between specific cell types and play a key role in the regulation of normal tissue development, remodeling, and degradation. Members of this family have been implicated in neurodegenerative and neuroinflammatory, as well as in muscular-skeletal, cardiovascular, respiratory and renal diseases, and cancer. Several metalloproteinases have been associated with schizophrenia. In our previous study of the pedigree from a genetic isolate of Spanish origin in Puerto Rico, we identified a schizophrenia susceptibility locus on chromosome 5p13 containing ADAMTS12. This gene, therefore, is not only a functional but also a positional candidate gene for susceptibility to the disorder. In order to examine possible involvement of ADAMTS12 in schizophrenia, we performed mutation analysis of the coding, 5'- and 3'-untranslated, and putative promoter regions of the gene in affected members of the pedigree and identified 18 sequence variants segregated with schizophrenia. We then tested these variants in 135 unrelated Puerto Rican schizophrenia patients of Spanish origin and 203 controls and identified the intronic variant rs256792 (P = 0.0035; OR = 1.59; 95% CI = 1.16-2.17) and the two-SNP haplotype rs256603-rs256792 (P = 0.0023; OR = 1.62; 95% CI = 1.19-2.21) associated with the disorder. The association remained significant after correction for multiple testing. Our data support the hypothesis that genetic variations in ADAMTS12 influence the risk of schizophrenia.

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Crossref · 10.1007/s12017-012-8169-y

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  • Findings from genetic association and GWAS analyses suggest that several metzincin protease genes, including ADAMTSL3, ADAMTS12, ADAMTS-16, ADAM22, and MMP16, may confer vulnerability to schizophrenia.

    “First, converging results from several recent genetic association and genome-wide association studies indicate that genes encoding for a number of metzincin metalloproteases may represent vulnerability factors for SZ.”

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Authors
Bespalova, I. N., Angelo, G. W., Ritter, B. P., Hunter, J., Reyes-Rabanillo, M. L., Siever, L. J., & Silverman, J. M.
Affiliations
  • James J. Peters VA Medical Center (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • VA Caribbean Healthcare System (PR)
Corresponding author
Bespalova, Irina N.
Venue
NeuroMolecular Medicine
Published
2012-02-10
Volume
14
Issue
1
Pages
53-64
ISSN
  • 1535-1084 (ISSN-L)
  • 1559-1174
OpenAlex
W2071291115
Cited by
14
References
107
Citations by year
2026: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 1
FWCI
0.91
Type
journal article
Language
en
Open access
closed
Locations
  • NeuroMolecular Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Alliance for Research on Schizophrenia and Depression
  • National Institute of Mental Health (R03MH082134)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
ADAMTS12, schizophrenia, genetic susceptibility, metalloproteinases, haplotype association, intronic variants, Puerto Rican patients, positional candidate genes
MeSH terms
ADAMTS Proteins, Base Sequence, DNA Mutational Analysis, Exons, Female, Haplotypes, Hispanic or Latino, Humans, Introns, Male, Molecular Sequence Data, Pedigree, Promoter Regions, Genetic, Puerto Rico, Risk, Schizophrenia, Genetic Variation, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, ADAM Proteins

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