Impacto de polimorfismos nos genes MAOA e MAOB em fenótipos associados à aprendizagem escolar

Abstract

School learning difficulties, such as dyscalculia and dyslexia, are important predictors of outcomes in adult life, such as salary, employability, emotional balance, etc. They are influenced by factors such as intelligence, socioeconomic status, quality of education, genetics, among others. Specifically in math achievement, there is also the influence of math anxiety (MA). Some metabolic pathways have been previously investigated in learning disabilities, including the effect of some genes involved in neurotransmitter metabolism. Two important enzymes are MAO-A (MAOA, the gene) and MAO-B (MAOB, the gene): greater enzymatic activity implies a shorter half-life of neurotransmitters, which these enzymes degrade (dopamine, serotonin, noradrenaline). In this study, the effects of two functional polymorphisms (MAOA_LPR and MAOB rs1799836) were investigated. In MAOA_LPR, 3R allele confers low activity (L, low activity), while 3.5R and 4R alleles confer high activity (H, high activity). Because these genes map to the X chromosome, girls can have the H/H, H/L, and L/L genotypes, while boys can only have the H/- or L/- genotypes. In MAOB rs1799836, the G allele confers low enzyme activity and the A allele confers high enzymatic activity. The genotypes are G/G, G/A and A/A in girls and G/- or A/- in boys. A total of 580 children aged between 7 and 12 years, studying from the 3rd to the 5th year in schools in Belo Horizonte and Porto Alegre were evaluated. Children were assessed for intelligence (Raven's Coloured Progressive Matrices), school performance (TDE Spelling and TDE Arithmetic), transcoding (Arabic Numerals Dictation), MA (Math Anxiety Questionnaire: MAQ-A: self-efficacy; MAQ-B: attitudes towards mathematics; MAQ-C: unhappiness towards mathematics; and MAQ-D: anxiety towards mathematics). The INSE (Indicador de Nível Socioeconômico) was used as a measure of the socioeconomic status of the schools. Significant differences were found between sexes, with boys presenting higher averages for intelligence and transcoding, and girls presenting higher averages for MA (MAQ-A) and better performance for spelling. Direct effects of genotypes were statistically significant for spelling and transcoding in the hole sample. No significant effects of sex or genotype on arithmetic performance were found. The interaction between genotype and sex was statistically significant for MA (MAQ-D): girls with a low MAOA enzymatic activity genotype had greater MA (MAQ- D). In MAOB, boys with lower enzymatic activity had lower MA (MAQ-D). The interaction between these genes was evaluated using model-based multifactor dimensionality reduction (MB-MDR). The combination of MAOA_LPR H/L and MAOB rs1799836 A/A + A/- genotypes was associated with a low risk of MA. In boys, the combination of MAOA_LPR L/- and MAOB rs1799836 G/- genotypes was associated with a lower risk of MA. Thus, a gender-dependent MAOA and MAOB effect is observed in MAQ-D and gender effects on intelligence in MAQ-A. These results provide a better understanding of the neurobiology of MA and the relationship between MAO-A and MAO-B enzymatic activities and the development of MA, as well as the role of sex in modifying the effect of genotype.