Predictive power of HLA-DQB1∗ to identify narcoleptic patients

Abstract

Introduction The determination of HLA class II genotype is widely used to confirm the diagnosis of Narcolepsy without (N) or with Cataplexy (NC). The use of HLA genotyping in clinical diagnosis is reliable and is a contributing factor to the reinforcement of the wide acceptance of the hypothesis of autoimmune origin for Narcolepsy. We evaluate the contribution of genetic markers (HLA) in the differential diagnosis between narcolepsy with and without Cataplexy and their relevance in the context of our population (Northern Portugal). Materials and methods A cohort of 53 patients with Narcolepsy with Cataplexy (NC) or without (N) was studied. Patients followed up to the Outpatient Sleep Clinic of Hospital Santo Antonio/CH Porto were assessed by clinical, night sleep polygraphic recording, MSLT on the following day. Blood sampling for HLA-DQB1 ∗ analysis was performed after informed consent. The genotyping was achieved by using a PCR-Sequence Specific Primer (SSP) methodology. Control Population (CP) comprised 206 reportedly healthy individuals from the same geographic origin. Data from laboratory parameters was confronted with the clinical diagnostic hypothesis. Patients’ clinical reevaluation was considered if phenotype-genotype did not match. Results Of the 53 patients, 14 were classified as N and 39 as NC. The frequency of HLA-DQB1 ∗ 06:02 allele was overrepresented in N and NC patients (43% and 69%, respectively) when compared with the control population (16%) – p value = 1.38 × 10–12 for NC. Interestingly the frequency of the HLA- DQB1 ∗ 03 allele was decreased in NC patients (36% NC vs. 56% CP, p = 0.01917). No differences were found in other DQB1 ∗ 06 frequencies between the cohort of patients and the control population. Conclusion The HLA-DQB1 ∗ 06:02 allele, a susceptibility factor for other autoimmune disorders, was confirmed as the most important susceptibility allele to NC in our population. The frequency of this allele in our NC patients (69%) is within the range of other studies. Such values pointed out to 11.8 OR for NC comparing with 3.9 OR for N patients. These findings point out to the relevance of the allele DQB1 ∗ 0602 in this sleep entity and on the autoimmune involvement in the picture of Narcolepsy–Cataplexy.