title: The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia.
abstract: The underlying pathophysiology of primary polydipsia in schizophrenia (SCZ) is poorly understood. Our previous study, however, suggested that this condition may have a genetic component [Shinkai et al 2003 Am J Med Genet 119B 7-12]. Orexins, also called hypocretins, play an important role in feeding and drinking behavior. Administration of orexin in rats has been shown to induce increased water intake with a longer-lasting effect than angiotensin II, which is also known as a potent dipsogen. Meerabux et al. [2005 Biol Psychiatry 58 401-407] reported an association between the 408Val allele of the orexin 1 receptor (HCRTR1) gene and polydipsia-hyponatremia in a sample of Japanese patients with SCZ. In the present study, we attempted to replicate the findings of Meerabux et al. in an independent Japanese case-control sample. Our sample included 312 patients with SCZ (DSM-IV) (65 with polydipsia and 247 without polydipsia). We also observed an association between the HCRTR1 Ile408Val polymorphism and polydipsia (genotype distribution: chi2 = 9.85, df = 2, P = 0.007). Meerabux et al. (2005) previously demonstrated an association between the 408Val allele of the HCRTR1 gene and polydipsia. In contrast with Meerabux et al. study, we found that the 408Ile allele was associated with polydipsia in our sample (chi2 = 8.00, df = 1, P = 0.0047; OR = 0.53; 95%CI = 0.34-0.83). How either allele contributes to the development of polydipsia in SCZ is unclear at this stage. It is possible that Ile408Val polymorphism is a non-functional marker that lies in linkage disequilibrium with an as-yet undetected functional variant. In any case, our results support the hypothesis that the HCRTR1 Ile408Val polymorphism may confer susceptibility to polydipsia in SCZ. Further studies examining the association between the orexin system and polydipsia in SCZ are warranted.
authors.affiliation: Department of Psychiatry, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukunaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinkai
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hori
authors.forename: Kensuke
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakata
authors.forename: Yui
authors.initials: Y
authors.lastname: Naoe
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Chima
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohmori
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007010:Hyponatremia / Q000209:etiology / Q000235:genetics*; D007532:Isoleucine; D008297:Male; D008875:Middle Aged; D064446:Orexin Receptors; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018013:Receptors, Neuropeptide / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*; D013894:Thirst / Q000502:physiology; D014633:Valine
chemical_list: C578630:HCRTR1 protein, human; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D007532:Isoleucine; D014633:Valine