Association Between Serum Orexin-A And Orexin-2Receptor Genetic Polymorphism And Primary Insomnia In Patients

Objective:To investigate the relationship of serum Orexin-A and gene polymorphism of OX2Rreceptor in patiens with primary insomnia.Methods:Primary insomnia group was comprised of the patients with chronic insomnia diseasewho had visited neurology sleep disorders clinic in Qianfoshan Hospital between2012March and July2013. Inclusion criteria: The diagnosis standards of Primary insomnia wasbased on the diagnostic and statistical manual of mental disorders (DSM-Ⅳ) of theUSA Psychiatric Association. We assessed patients’ sleep quality according tothe Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) who takethe Pittsburgh Sleep Quality Scale (PSQI) score≥7points, excluding the serious physicaldiseases, mental disorders and sleep-related central nervous system disease caused by sleepdisorders medical.128primary insomnia patients (76males,52females; mean age50.16±13.9years), meeting above inclusion criteria, were included in primary insomniagroup.82volunteers (39males,43females; mean age47.64±18.5years) whose PittsburghSleep Quality Scale (PSQI) score <7points, from our hospital physical examination centerexamination during the same period, were included in control group. All persons werecollected fasting blood from ulnar vein before8am. Serum orexin-A was detected byenzyme-linked immunoadsordent assay(ELISA) and352C>T,355C>A and1246G>Asingle nucleotide polymorphism of OX2R receptor gene were examined by polymerasechain reaction (PCR) and gene sequencing technology.Results:PSQI total scores of primary insomnia group was significant difference from that ofcontrol group. We found significant difference in the symptoms of difficulty falling asleep, daytime dysfunction and sleep maintenance difficulty of Pittsburgh Sleep Quality Scalebetween primary insomnia group and control group. But Epworth Sleepiness Scale scoreshowed no significant difference, indicating patients with primary insomnia had mildsymptoms of daytime sleepiness. Further study showed that levels of serum orexin-A inprimary insomnia group were significantly higher than that in control group, revealedserum orexin-A was correlated with the primary insomnia and participated in maintainingarousal, which may be one of the reasons for the insomnia patients who appeared lessdaytime sleepiness. In addition, we studied single nucleotide mutation in OX2R gene. Thepreliminary results showed there was no gene mutation in352C>T and355C>A of OX2Rgene，however we found that compared with control group, the single nucleotide mutationfrequency of1246G>A in OX2R gene from primary insomnia group was two timeshigher,and serum orexin-A level in GA genotypes were higher than that in GG genotype.Our study showed OX2R1246G>A gene polymorphism was association with primaryinsomnia.Moreover,high level of serum orexin-A in patients with GA genotypes illustratedthat1246G>A single nucleotide mutation affected the function of OX2R, leading to thecompensatory increase of orexin-A, which may be involved in the formation of primaryinsomnia.Conclusion:Orexin-A and OX2R gene polymorphisms were interrelated with primaryinsom-nia.1246G>A single nucleotide mutation affected OX2R function, which may beinvolved in the formation of primary insomnia.