Genetic Variations in the ADAMTS12 Gene are Associated with Schizophrenia in Puerto Rican Patients of Spanish Descent
Autor: | Ben P. Ritter, Irina N. Bespalova, Gary Angelo, María L Reyes-Rabanillo, Larry J. Siever, Jeremy M. Silverman, Jason Hunter |
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Rok vydání: | 2012 |
Předmět: |
Male
Risk DNA Mutational Analysis Molecular Sequence Data Biology Bioinformatics Polymorphism Single Nucleotide White People Cellular and Molecular Neuroscience ADAMTS Proteins Genetic variation medicine Humans Genetic Predisposition to Disease Promoter Regions Genetic Gene Genetics Base Sequence Puerto Rico Haplotype Genetic Variation Chromosome Cancer Exons Hispanic or Latino medicine.disease Introns Pedigree ADAM Proteins Haplotypes Neurology Schizophrenia Mutation testing Molecular Medicine Female Genetic isolate |
Zdroj: | NeuroMolecular Medicine. 14:53-64 |
ISSN: | 1559-1174 1535-1084 |
Popis: | 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. |
Databáze: | OpenAIRE |
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