Abstract
A functional polymorphism in the promoter region of the DRD2 gene has been found to be associated with schizophrenia in Japanese1,2 and Swedish populations.3 We attempted to replicate these findings in a genetically homogenous Portuguese population using a family-based study design. Analysis of 78 trios revealed evidence for association between the −141 C Ins allele and schizophrenia using the haplotype relative risk (HRR) method (χ2 = 9.30, P = 0.0023). Further examination of this sample using an alternative family-based association analysis method, the transmission disequilibrium test (TDT), of 33 informative matings from the Portuguese trios provided evidence for an allelic association and linkage disequilibrium between the insertion allele and schizophrenia (χ2 = 8.76, P = 0.0031). These consistent results using two alternative family-based association analysis methods replicate the findings of previous reports, and thus further implicate a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia.
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References
Arinami T, Gao M, Hamaguchi H, Toru M . A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia Hum Mol Genet 1997 6: 577–582
Ohara K, Hagai M, Tami K, Nakamura Y, Ino A, Ohara K . Functional polymorphism of −141 C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia Psychiatry Res 1998 81: 117–123
Jonsson EG, Nothen MM, Neidt H, Forslund K, Rylander G, Mattila-Evenden M et al. Association between a promoter polymorphism in the dopamine D2 receptor gene and schizophrenia Schizophr Res 1999 40: 31–36
Gottesman II, Shields J . Schizophrenia: The Epigenetic Puzzle Cambridge University Press: Cambridge, UK 1982
McGuffin P, Owen MJ, Farmer AD . The genetic basis of schizophrenia Lancet 1995 346: 678–682
Tsuang MT . Genetic epidemiology of schizophrenia: review and reassessment Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 1998 14: 405–412
Falk CT, Rubinstein P . Haplotype relative risk: an easy reliable way to construct a proper control sample for risk calculations Ann Hum Genet 1987 51: 227–233
Terwilliger JD, Ott J . A haplotype-based ‘haplotype relative risk’ approach to detecting allelic associations Hum Hered 1992 42: 337–346
Spielman RS, McGinnis RE, Ewens WJ . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus Am J Hum Genet 1993 52: 506–516
Ewens WJ, Spielman RS . The transmission/disequilibrium test: history, subdivision, and admixture Am J Hum Genet 1995 57: 455–464
Palermo-Neto J . Dopaminergic systems: dopamine receptors Psych Clin N Am 1997 20: 705–721
Breen G, Brown J, Maude S, Fox H, Collier D, Li T et al. −141 C del/ins polymorphism of the dopamine receptor 2 gene is associated with schizophrenia in a British population Am J Med Genet 1999 88: 407–410
Li T, Arranz M, Aitchison KJ, Bryant C, Liu X, Kerwin RW et al. Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia Schizophr Res 1998 32: 87–92
Tallerico T, Ulpian C, Liu IS . Dopamine D2 receptor promoter polymorphism: no association with schizophrenia Psychiatry Res 1999 85: 215–219
Stober G, Jatzke AH, Jungkunz G, Knapp M, Mossner R, Riederer P et al. Insertion/deletion variant (−141 C Ins/Del) in the 5′ regulatory region of the dopamine D2 receptor gene: lack of association with schizophrenia and bipolar affective disorder J Neural Transm 1998 105: 101–109
Arranz MJ, Munro J, Li T, Collier DA, Kirov G, Kerwin RW . A polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and drug response: association studies Schizophr Res 1998 29: 127
Pato CN, Schindler KM, Pato MT . Genetic isolates and behavioural gene searches Encyclopedia of Human Genetics (in press)
Pato CN, Azevedo MH, Pato MT, Kennedy JL, Coelho I, Dourado A et al. Selection of homogenous populations for genetic study: the Portugal genetics of psychosis project Am J Med Genet 1997 74: 286–288
Seeman P . Dopamine receptor sequences: therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4 Neuropsychopharmacology 1992 7: 261–284
Costa C . Etnologia dos Acores Logoa: S Miguel 1991
Nurnberger JI Jr, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG, Harkavy-Friedman J et al. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative Arch Gen Psychiatry 1994 51: 849–859
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Schindler, K., Pato, M., Dourado, A. et al. Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population. Mol Psychiatry 7, 1002–1005 (2002). https://doi.org/10.1038/sj.mp.4001126
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DOI: https://doi.org/10.1038/sj.mp.4001126