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SNP-SNP interactions in the BDNF, COMT, CBR1 and CCK genes, associated with post-traumatic stress disorder in urban residents of Itagüí, Colombia
Interacciones SNP-SNP en los genes BDNF, COMT, CBR1 y CCK asociadas al trastorno de estrés postraumático en la población urbana de Itagüí, Colombia
DOI:
https://doi.org/10.15446/revfacmed.v68n4.77723Palabras clave:
Stress Disorders Post-Traumatic, Extinction Psychological, Polymorphism Single Nucleotide, Risk Ratio (en)Trastornos por Estrés Postraumático, Extinción Psicológica, Polimorfismo de Nucleótido Simple, Factores de Riesgo (es)
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Introduction: Single nucleotide polymorphisms (SNPs) in the BDNF, COMT, CBR1 and CCK genes have been associated with the process of fear extinction in humans. Since fear extinction plays a key role in recovering from psychological trauma, there is a possibility that these genes modulate the risk of developing post-traumatic stress disorder (PTSD).
Objective: To assess unilocus and multilocus associations between SNPs in the BDNF, COMT, CBR1 and CCK genes and the risk of developing PTSD.
Materials and methods: 129 inhabitants of the municipality of Itagüí, Colombia, who had experienced psychological trauma at least once, were genotyped for these polymorphisms (38 cases of PTSD and 91 controls). Logistic regression was used to perform unilocus and multilocus association tests for single SNPs and existing SNP-SNP genotypic combinations.
Results: No unilocus associations were found, but interactions between the BDNF and CBR1 genes and between the COMT and CCK genes were observed. Of these interactions, the genotypic combinations that behaved as risk factors were AG-AA (OR=13.52, p<0.05) in the BDNF-CBR1 interaction, and TC-AA (OR=13.70, p<0.05) in the CCK-COMT interaction.
Conclusions: The two pairs of interacting polymorphisms found in this study could act additively and generate a greater risk of developing PTSD after suffering psychological trauma. People who have a single allele have a lower risk of developing PTSD than those who have two alleles in the interacting genes.
Introducción. Los polimorfismos de un solo nucleótido (SNP, por su sigla en inglés) en los genes BDNF, COMT, CBR1 y CCK han sido asociados con el proceso de extinción del miedo en humanos. Dado que la extinción del miedo es clave para la recuperación del trauma psicológico, es posible que estos genes modulen el riesgo de desarrollar trastorno de estrés postraumático (TEPT).
Objetivo. Evaluar las asociaciones unilocus y multilocus entre los SNP en los genes BDNF, COMT, CBR1 y CCK y el riesgo de desarrollar TEPT.
Materiales y métodos. 129 habitantes del municipio de Itagüí, Colombia, que habían experimentado trauma psicológico al menos una vez, fueron genotipificados para estos polimorfismos (38 casos de TEPT y 91 controles). Se realizaron pruebas de asociación unilocus y multilocus por regresión logística para SNP únicos y las combinaciones genotípicas SNPSNP existentes.
Resultados. No se encontraron asociaciones unilocus, pero se observaron interacciones entre BDNF y CBR1, y CCK y COMT. De estas interacciones, las combinaciones genotípicas que se comportaron como factores de riesgo fueron AG-AA (OR=13.52, p<0.05) de BDNF-CBR1 y TC-AA (OR=13.70, p<0.05) de CCK-COMT.
Conclusiones: Los dos pares de polimorfismos en interacción encontrados en el presente estudio podrían actuar de forma aditiva y generar un mayor riesgo de desarrollar TEPT después de sufrir trauma psicológico. Quienes portan un solo alelo tienen un menor riesgo de desarrollar el trastorno que quienes portan dos alelos en genes que interactúan entre sí.
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