Estudio de Asociaciòn de los Genes DGKH (rs1170169, rs9525580), DAT1 (3’UTR-VNTR 40pb), DRD4 (VNTR EXON III 48pb) y CDH13 (rs7187223, rs11646411) en Pacientes Infantiles Colombianos que Presentan Diagnòstico de Trastorno de Comportamiento

Abstract

Behavioral disorder diseases have a prevalence in children of 4.8% -7.4% and in girls of 2.1% - 3.2% and in adolescents it is 1.5% - 3.4% (1 ). In Colombia, the prevalence of psychiatric disorders is between 12% and 29% (2). These are the main cause of consulting psychologists or psychiatrists on the part of children and young people who are in the period of maturation and complete development of the Prefrontal cortex (3,4,5). Despite these statistics, many studies on childhood behavioral disorders that attempt to explain biologically these pathologies have not been developed in Colombia (3,4,2). In this case-control study, a methodology was developed to analyze the association of six genetic markers of the DGKH genes (rs1170169, rs9525580), DAT1 (3'UTR-VNTR 40pb), DRD4 (VNTR EXON III 48pb) CDH13 (Rs7187223, rs11646411) which have been related to the positive diagnosis of behavioral disorder diseases (ADHD, OCD and ASD). These studies have been chosen based on the analysis of different Genome Whole Association Studies (GWAS) and case control studies (6,3,4,7), as well as the studies on their influence on the Development of the prefrontal cortex and previous studies in Colombia (8). A total of 102 individuals (51 cases and 51 controls, gender-matched and ± 1 year-old) were genotyped in the central region of Colombia, with a mean age of 11.09 years, 55.88% of the male gender And 34.31% of the female gender. For genotyping, the techniques of allelic identification, conventional PCR and real-time PCR (TaqMan probes) were used, with which the allelic and genotype frequencies of the selected variants, Hardy Weinberg, Test of Fisher (p-value) and Odds Ratio. As a result we found that the markers of rs1170169, rs9525580, 3'UTR-VNTR 40pb, rs7187223 and rs11646411 are not associated with childhood behavioral disorders in the central region of Colombia, however consult with a larger study population. Markers of the CDH13 gene (rs7187223 and rs11646411), since they present a significant Odds Ratio (OR = 1,531 and OR = 0,327 respectively). On the other hand the DRD4 gene marker (VNTR EXON III 48pb) was found for the 4R-4R genotype significant differences (the association value of 0.0091 and OR of 0.2825), demonstrated it of what this genotype is of the Protection for the population study It was also verified that the 4R allele of this VNTR also has a significant association (p = 0.015 and OR = 0.4783 (95% CI)) with protection of the behavioral disorders studied, Study was found that alleles Uncommon (including the 7R allele) may be at risk, while the 4R allele confers protection, especially with the 4R-4R genotype.