Sleep disorders diagnosis by genetic assessment

Abstract

Diagnosis of Sleep Disorders (SD) is frequently a difficult task. Environmental and genetic factors influence the clinical SD phenotype masking its correct identification. The definition of such factors will help the physicians to easily classify SD. Accordingly a better treatment for such disorders should be obtained. The objective of the present work is to identify, on a cohort of SD patients, the possible genetic factors involved. Four hundred and twenty-one SD patients were assessed at the Out Patient Sleep Clinic of Hospital Santo António/CH Porto – by means of clinical history, physical and neurological evaluation, night sleep polygraphic EEG-Video recording (EEG, EOG, EMG – chin and L Limbs; Respiratory effort; O 2 saturation; EKG; snoring). For Narcolepsy without (N) or with Cataplexy (NC) and for Hypersomnia (H) qualification/quantification a MSLT was performed on the day after night registration. Blood venous sample was taken after informed consent. Ethical approval was obtained for research studies. For the purpose of distinction between diverse Sleep Disorders HLA–DRB1 ∗ was genotyped using a PCR-Sequence Specific Primer (SSP) methodology. A control population (223 individuals) was matched to age, gender, ethnicity and geographical origin. Statistical analysis was performed and the phenotypic frequencies were evaluated by chi- square of 2 × 2 contingency tables. Odds Ratios and their respective 95% confidence interval were calculated. Values of p < 0.05 were considered as statistically significant. From the 421 SD patients studied 302 were classified as obstructive sleep apnea syndrome (OSAS); 64 as H; 37 NC and 16 N. Significant values ( p < 0.05) of HLA–DRB1 ∗ alelles were found to OSAS: HLA-DRB1 ∗ 09 (1% OSAS vs. 6% PC); NC: HLA-DRB1 ∗ 13 (14% NC vs. 30% PC) and 15 (76% NC vs. 21% PC); N: HLA-DRB1 ∗ 15 (44% N vs. 21% PC); H: HLA–DRB1 ∗ 03 (33% H vs. 15% PC). Our studies emphasize that the HLA–DRB1 ∗ genetic characterization of SD patients may identify different profiles. The results point out to the identification of susceptibility alleles, HLA–DRB1 ∗ 15 for N and NC and HLA–DRB1 ∗ 03 for Hypersomnia. The frequencies of HLA–DRB1 ∗ 09 in OSAS and of HLA–DRB1 ∗ 13 in NC indicate that these alleles may act as protective factors. These findings point to the value of immunogenetic approach to a better understanding of the pathophysiology of SD and to a better classification of patients with sleep disorders. ∗ Studies on SAOS were granted by a CESPU Project .