BACKGROUND: The gap junction subunit connexin permits direct intercellular exchange of ions and molecules including glutamate, and plays an important role in the central nervous system. The connexin 40 (Cx40) and connexin 50 (Cx50) genes are located on chromosome 1q21.1, a region strongly linked with schizophrenia. These lines of evidence suggest that Cx40 and Cx50 may play a role in schizophrenia. METHODS: Using an allele-specific PCR assay, four polymorphisms each were genotyped for Cx40 and Cx50 in 190 Caucasian patients with schizophrenia and 190 controls matched for sex, age and ethnicity. Following up, Cx50 rs989192 and rs4950495 were investigated in 99 Canadian and 163 Portuguese trios and nuclear families with schizophrenia probands. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) block identification was carried out with HaploView, and association analysis for alleles and haplotypes with a permutation test of 10 000 simulations was carried out using the UNPHASED software program. RESULTS: Distributions of genotype frequencies of all markers were in Hardy-Weinberg equilibrium in Caucasian patients, controls and families. One rs989192-rs4950495 LD block was found in patients but not in controls. We found a significant association between the Cx50 rs989192-rs4950495 haplotype and schizophreniay (chi(2) = 29.55, p<0.01). The A-C haplotype had a higher frequency in patients (chi(2) = 7.153, p<0.01). Family studies also showed that the A-C haplotype was transmitted more often to patients with schizophrenia (chi(2) = 8.43, p<0.01). No association of Cx40 with schizophrenia was found for allele, genotype or haplotype analyses. CONCLUSIONS: Our matched case-control and family study indicate that Cx50, but not Cx40, may play a role in the genetic susceptibility to schizophrenia.
BACKGROUND: The gap junction subunit connexin permits direct intercellular exchange of ions and molecules including glutamate, and plays an important role in the central nervous system. The connexin 40 (Cx40) and connexin 50 (Cx50) genes are located on chromosome 1q21.1, a region strongly linked with schizophrenia. These lines of evidence suggest that Cx40 and Cx50 may play a role in schizophrenia. METHODS: Using an allele-specific PCR assay, four polymorphisms each were genotyped for Cx40 and Cx50 in 190 Caucasian patients with schizophrenia and 190 controls matched for sex, age and ethnicity. Following up, Cx50rs989192 and rs4950495 were investigated in 99 Canadian and 163 Portuguese trios and nuclear families with schizophrenia probands. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) block identification was carried out with HaploView, and association analysis for alleles and haplotypes with a permutation test of 10 000 simulations was carried out using the UNPHASED software program. RESULTS: Distributions of genotype frequencies of all markers were in Hardy-Weinberg equilibrium in Caucasian patients, controls and families. One rs989192-rs4950495 LD block was found in patients but not in controls. We found a significant association between the Cx50rs989192-rs4950495 haplotype and schizophreniay (chi(2) = 29.55, p<0.01). The A-C haplotype had a higher frequency in patients (chi(2) = 7.153, p<0.01). Family studies also showed that the A-C haplotype was transmitted more often to patients with schizophrenia (chi(2) = 8.43, p<0.01). No association of Cx40 with schizophrenia was found for allele, genotype or haplotype analyses. CONCLUSIONS: Our matched case-control and family study indicate that Cx50, but not Cx40, may play a role in the genetic susceptibility to schizophrenia.
Authors: J Ekelund; I Hovatta; A Parker; T Paunio; T Varilo; R Martin; J Suhonen; P Ellonen; G Chan; J S Sinsheimer; E Sobel; H Juvonen; R Arajärvi; T Partonen; J Suvisaari; J Lönnqvist; J Meyer; L Peltonen Journal: Hum Mol Genet Date: 2001-07-15 Impact factor: 6.150
Authors: Hreinn Stefansson; Dan Rujescu; Sven Cichon; Olli P H Pietiläinen; Andres Ingason; Stacy Steinberg; Ragnheidur Fossdal; Engilbert Sigurdsson; Thordur Sigmundsson; Jacobine E Buizer-Voskamp; Thomas Hansen; Klaus D Jakobsen; Pierandrea Muglia; Clyde Francks; Paul M Matthews; Arnaldur Gylfason; Bjarni V Halldorsson; Daniel Gudbjartsson; Thorgeir E Thorgeirsson; Asgeir Sigurdsson; Adalbjorg Jonasdottir; Aslaug Jonasdottir; Asgeir Bjornsson; Sigurborg Mattiasdottir; Thorarinn Blondal; Magnus Haraldsson; Brynja B Magnusdottir; Ina Giegling; Hans-Jürgen Möller; Annette Hartmann; Kevin V Shianna; Dongliang Ge; Anna C Need; Caroline Crombie; Gillian Fraser; Nicholas Walker; Jouko Lonnqvist; Jaana Suvisaari; Annamarie Tuulio-Henriksson; Tiina Paunio; Timi Toulopoulou; Elvira Bramon; Marta Di Forti; Robin Murray; Mirella Ruggeri; Evangelos Vassos; Sarah Tosato; Muriel Walshe; Tao Li; Catalina Vasilescu; Thomas W Mühleisen; August G Wang; Henrik Ullum; Srdjan Djurovic; Ingrid Melle; Jes Olesen; Lambertus A Kiemeney; Barbara Franke; Chiara Sabatti; Nelson B Freimer; Jeffrey R Gulcher; Unnur Thorsteinsdottir; Augustine Kong; Ole A Andreassen; Roel A Ophoff; Alexander Georgi; Marcella Rietschel; Thomas Werge; Hannes Petursson; David B Goldstein; Markus M Nöthen; Leena Peltonen; David A Collier; David St Clair; Kari Stefansson Journal: Nature Date: 2008-09-11 Impact factor: 49.962
Authors: Noortje Wa Van de Kerkhof; Ilse Feenstra; Frank Mma van der Heijden; Nicole de Leeuw; Rolph Pfundt; Gerald Stöber; Jos Im Egger; Willem Ma Verhoeven Journal: Neuropsychiatr Dis Treat Date: 2012-07-12 Impact factor: 2.570