Low HLA DQB1 0602 in portuguese narcoleptics

Abstract

Narcolepsy is a rare sleep disorder characterized by episodes of excessive sleepiness. Symptoms such as cataplexy sleep paralysis, REM sleep onset and hypnopompic or hypnagogic hallucinations can also occur. The ICSD-2 classifies this sleep disturbance in several subtypes, namely: Narcolepsy with Cataplexy, Narcolepsy without cataplexy, Narcolepsy due to medical condition and Narcolepsy non-specific. The diagnosis implies the existence of excessive sleepiness with or without cataplexy, and the recording of two SOREM’s (Sleep Onset Rapid Eye Movement) in the Multiple Sleep Latency Test (MSLT). The symptoms described above should also be considered. In Brazil HLA DQB1*0602 allele is prevalent in 95% of patients with cat- aplexy, and has been highlighted in less than 50% of patients without cataplexy (Coelho F., et al., 2010); these data are in line with other international data. In Portugal there are about 47 in every 100 000 inhabitants with Narcolepsy (Ohayon et al., 2002), i.e., similar to other European countries, however HLA DQB1*0602 prevalence has been found around 60% in Narcolepsy with cataplexy (Viegas et al. 2013). OBJECTIVES The aim of this study was to enlarge the database to other regions of the country in order to better determine the prevalence of HLA DQB1 0602 and HLA DRB1 1501 in cases of Narcolepsy with (NC) and without cataplexy (NnoC). 183 patients were selected; 117 with cataplexy and 66 without cataplexy. All patients were diagnosed according to standard criteria (ICSD2), using a clinical interview, a cataplexy questionnaire and Type 1 PSG followed by MSLT. HLA typing was performed in officially recognized laboratories. Data were obtained in Center and South Portuguese regions. 54% of the NC are males against 42% of the NnoC. The statistical differences between the 2 groups were: average age of the symptoms onset (24.46 years for NC and 26.81 for NnoC; diagnostic delay took a mean of 16 years for NC while for NnoC it was only 8.29 years. Prevalence of sleep paralysis and hallucinations are statistically different among groups: 44% of the narcoleptic with cataplexy have sleep paralysis against 24.5 of the narcoleptic without cataplexy; 60% of the narcoleptic with cataplexy have hallucinations when compared to 28% of the patients without cataplexy. The mean latency in the MSLT is low for both groups: 4.11 ± 2.52 min for NC and 4.32 ± 2.06 min for NnoC. The patients with cataplexy had an average of 1.98 ± 1.51 SOREMS and those without cataplexy have about 2.16 ± 1.057 SOREMS. The HLA DQB1 0602 was more prevalent in NC: 51% for the NC have HLA DQB10602, while only 31% of the NnoC have this allele. The HLA DRB11501 is prevalent in 42% of the subjects with cataplexy and 25% of those without cataplexy. The low HLA prevalence of DQB1 0602 in NC in our population has so far no clear explanation. It is tempting to assume that the high miscegenation started many centuries ago - it’s a possible explanation. In a National study of HLA prevalence clear differences in allele frequency do exist between North, Center and South regions, in spite of the relatively short differences in KM (Spinola et al. 2005). Furthermore these authors propose a marked influence of African and European genes, with African genes more prevalent in South regions. The high prevalence of HLA DQB1 0602 in NC detected in a São Paulo, Brazilian study renders this explanation eventually difficult, taking into account many similarities between both countries. However 2 aspects may be open for discussion: the reduced number of brazilian cases and the possibility that in Brazil there are strong territorial differences. The questions raised by this study deserve further research. (1) Ohayon, M.M., Priest R.G., Zulley J., Smirne S., Paiva T. (2002). Prevalence of narcolepsy symptomatology and diagnosis in the European general population. Neurology, 58: 1826–1833. (2) Morrish E., King M.A., Smith I.E., Shneerson J.M. (2004). Factors associated with a delay in the diagnosis of narcolepsy. Sleep Medicine, 5: 37–41. (3) David A, Constantino F, Santos JM, Paiva T. Health-related quality of life in Portuguese patients with narcolepsy. Sleep Med. 2012 Jan 24. (4) Coelho F.M.S, Pradella-Hallinan M., Pedrazzoli M., Soares C.A.S., Fernandes G.B.P., Gonçalves A.L., Tufik S. & Bittencourt L.R.A. (2010). Traditional biomarkers in narcolepsy – experience of a brazilian sleep centre. Arq Neuropsiquiatr, 68 (5): 712 – 715. (5) Spínola H, Middleton D, Brehm A. (2005). HLA genes in Portugal inferred from sequence-based typing: in the crossroad between Europe and Africa. Tissue Antigens. 66(1):26–36.