Use of PCR with Sequence-specific Primers for High-Resolution Human Leukocyte Antigen Typing of Patients with Narcolepsy

Abstract

BackgroundNarcolepsy is a neurologic disorder characterized by excessive daytime sleepiness, symptoms of abnormal rapid eye movement (REM) sleep, and a strong association with HLA-DRB1*1501, -DQA1*0102, and -DQB1*0602. Here, we investigated the clinico-physical characteristics of Korean patients with narcolepsy, their HLA types, and the clinical utility of high-resolution PCR with sequence-specific primers (PCR-SSP) as a simple typing method for identifying DRB1*15/16, DQA1, and DQB1 alleles.MethodsThe study population consisted of 67 consecutively enrolled patients having unexplained daytime sleepiness and diagnosed narcolepsy based on clinical and neurological findings. Clinical data and the results of the multiple sleep latency test and polysomnography were reviewed, and HLA typing was performed using both high-resolution PCR-SSP and sequence-based typing (SBT).ResultsThe 44 narcolepsy patients with cataplexy displayed significantly higher frequencies of DRB1*1501 (Pc= 0.003), DQA1*0102 (Pc=0.001), and DQB1*0602 (Pc=0.014) than the patients without cataplexy. Among patients carrying DRB1*1501-DQB1*0602 or DQA1*0102, the frequencies of a mean REM sleep latency of less than 20 min in nocturnal polysomnography and clinical findings, including sleep paralysis and hypnagogic hallucination were significantly higher. SBT and PCR-SSP showed 100% concordance for high-resolution typing of DRB1*15/16 alleles and DQA1 and DQB1 loci.ConclusionsThe clinical characteristics and somnographic findings of narcolepsy patients were associated with specific HLA alleles, including DRB1*1501, DQA1*0102, and DQB1*0602. Application of high-resolution PCR-SSP, a reliable and simple method, for both allele- and locus-specific HLA typing of DRB1*15/16, DQA1, and DQB1 would be useful for characterizing clinical status among subjects with narcolepsy.

Identification of the Variations in the CPT1B and CHKB Genes Along with the HLA-DQB1*06:02 Allele in Turkish Narcolepsy Patients and Healthy Persons

“…Similarly, the mean SOREMP was also significantly less in HLA-DQB1*06:02-positive patients than HLA-DQB1*06:02-negative patients (Tables 1 and 2). However, some previous studies have not shown significant differences in MSLT and SOREMPs among the HLA-DQB1*06:02-positive and -negative patients (Woo et al, 2012). In general, however, our results are in line with previous findings (Mignot et al, 1999;Hong et al, 2006;Watson et al, 2010;Andlauer et al, 2012;Mignot et al, 2006).…”

HLA‐DQ association and allele competition in Chinese narcolepsy

“…The loss of hypocretin neurons can be documented through the measure of hypocretin‐1 in the cerebrospinal fluid (CSF) . In almost all populations, narcolepsy is strongly associated with DRB1*15:01‐DQA1*01:02‐DQB1*06:02 , suggesting an autoimmune mediation of the hypocretin cell loss. The human leucocyte antigen (HLA) association is even stronger when CSF hypocretin‐1 has been evaluated .…”

Narcolepsy type 1

“…Nocturnal sleep disturbance as was witnessed in our patient is usually present in a patient of narcolepsy with cataplexy and not seen in a subject without it. Two other tests with very limited applicability are human leukocyte antigen (HLA) typing[6] (HLA DQB1*0602 And HLA DQA1*0102) and measurement of cerebrospinal fluid hypocretin level,[7] which were not done in our patients.…”