Dados do Trabalho

Título

Narcolepsy type 1 and 2 in Brazil: a precision medicine approach

Introdução

Narcolepsy and idiopathic hypersomnia (IH) are the most significant central disorders of hypersomnolence. While HLA-DQB1*06:02 is the primary genetic risk factor for narcolepsy, other alleles have also been identified. However, data on these conditions in Brazil is limited, with previous studies not exploring HLA hirh resolution sequencing and hypocretin measurement, now considered a biomarker for NT1. Additionally, there is ongoing research to find a biomarker for diagnosing narcolepsy type 2 (NT2) and IH. Therefore, genetic studies in a diverse population like Brazil can provide valuable information on primary hypersomnias

Objetivo

This study aimed to investigate genetic characteristics associated with susceptibility or protection for narcolepsy and IH in the Brazilian population using Precison Medicine for diagnose of NT1 and NT2

Métodos

Diagnosis of narcolepsy and IH was based on the third version of the International Classification of Sleep Disorders, with sub-classification into NT1 and NT2 determined by the concentration of CSF hypocretin 1 using radioimmunoassay. High-resolution HLA sequencing for class I (A, B, and C) and class II (DPB1, DRB1, and DQB1) alleles was conducted using massive parallel sequencing. The study compared obtained data with the National Registry of Bone Marrow Donors (REDOME) database, matching by sex, self-declared ethnicity, and geographic location in a ratio of 1 case to 5 controls.

Resultados

The study included 43 narcolepsy patients and 215 controls, 15 NT1, 16 NT2 and 12 narcolepsy without hypocretin measurement. NT1 patients exhibited a higher frequency of the HLA-DQB1*06:02 allele compared to controls and NT2 patients (100% vs. 20% vs. 18.75%, respectively; p<0.001). Following DQB1*06:02, DRB1*15:03 was identified as the most common allele associated with NT1, forming a haplotype with an odds ratio of 14.47 compared to controls (95% CI: 4-53.1, p<0.005).DRB1*15:01 was not associated a significant risk after Bonferroni correction. All 43 patients presented at leat one risk alelle already described in literature. Variables beyond cataplexy were useful in differentiating NT1 from NT2.

Conclusões

This first Brazilian study on narcolpesy using precision medicine revealed that HLA-DQB1*06:02 is the main genetic risk factor for NT1 but not for NT2 with a higher frequency than previous reports . The DRB1*15:03 was more prevalent among NT1 Brazilian patients in this sample, suggesting the influence of African heritage.

Palavras -chave

narcolepsy, precision medicine, hypocretin, Brazil