title: 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.
abstract: BACKGROUND
  The HLA-DQB1*06:02 allele across all ethnic groups and the rs5770917 variation between CPT1B and CHKB genes in Japanese and Koreans are common genetic susceptibility factors for narcolepsy. This comprehensive genetic study sought to assess variations in CHKB and CPT1B susceptibility genes and HLA-DQB1*06:02 allele status in Turkish patients with narcolepsy and healthy persons.
  
  
  METHODS
  CHKB/CPT1B genes were sequenced in patients with narcolepsy (n=37) and healthy persons (n=100) to detect variations. The HLA-DQB1*06:02 allele status was determined by sequence specific polymerase chain reaction.
  
  
  RESULTS
  The HLA-DQB1*06:02 allele was significantly more frequent in narcoleptic patients than in healthy persons (p=2×10(-7)) and in patients with narcolepsy and cataplexy than in those without (p=0.018). The mean of the multiple sleep latency test, sleep-onset rapid eye movement periods, and frequency of sleep paralysis significantly differed in the HLA-DQB1*06:02-positive patients. rs5770917, rs5770911, rs2269381, and rs2269382 were detected together as a haplotype in three patients and 11 healthy persons. In addition to this haplotype, the indel variation (rs144647670) was detected in the 5' upstream region of the human CHKB gene in the patients and healthy persons carrying four variants together.
  
  
  CONCLUSIONS
  This study identified a novel haplotype consisting of the indel variation, which had not been detected in previous studies in Japanese and Korean populations, and observed four single-nucleotide polymorphisms in CHKB/CPT1B. The study confirmed the association of the HLA-DQB1*06:02 allele with narcolepsy and cataplexy susceptibility. The findings suggest that the presence of HLA-DQB1*06:02 may be a predictor of cataplexy in narcoleptic patients and could therefore be used as an additional diagnostic marker alongside hypocretin.
authors.affiliation: 1 Department of Medical Biology and Genetics, School of Medicine, Dokuz Eylül University , Inciralti, Izmir, Turkey .
authors.forename: Sultan
authors.initials: S
authors.lastname: Cingoz
authors.forename: Sinem
authors.initials: S
authors.lastname: Agilkaya
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Oztura
authors.forename: Secil
authors.initials: S
authors.lastname: Eroglu
authors.forename: Derya
authors.initials: D
authors.lastname: Karadeniz
authors.forename: Ahmet
authors.initials: A
authors.lastname: Evlice
authors.forename: Oguz
authors.initials: O
authors.lastname: Altungoz
authors.forename: Hikmet
authors.initials: H
authors.lastname: Yilmaz
authors.forename: Baris
authors.initials: B
authors.lastname: Baklan
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D002797:Choline Kinase / Q000235:genetics*; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005260:Female; D014644:Genetic Variation; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D009290:Narcolepsy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014421:Turkey
chemical_list: D017931:DNA Primers; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase; C542592:CHKB protein, human; D002797:Choline Kinase