Allelic Association Between a Ser-9-Gly Polymorphism in the Dopamine D3 Receptor Gene and Schizophrenia

Overview

Journal Hum Genet

Specialty Genetics

Date 1996 Jun 1

PMID 8641685

Citations 25

Authors

S Shaikh

D A Collier

P C Sham

D Ball

K Aitchison

H Vallada

I Smith

M Gill

R W Kerwin

Affiliations

Soon will be listed here.

Abstract

We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.

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References

Saha N, Tsoi W, Low P, Basair J, Tay J . Lack of association of the dopamine D3 receptor gene polymorphism (BalI) in Chinese schizophrenic males. Psychiatr Genet. 1994; 4(4):201-4. DOI: 10.1097/00041444-199400440-00002. View

Di Bella D, Catalano M, Strukel A, Nobile M, Novelli E, Smeraldi E . Distribution of the MscI polymorphism of the dopamine D3 receptor in an Italian psychotic population. Psychiatr Genet. 1994; 4(1):39-42. DOI: 10.1097/00041444-199421000-00006. View

Endicott J, Spitzer R, Fleiss J, Cohen J . The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry. 1976; 33(6):766-71. DOI: 10.1001/archpsyc.1976.01770060086012. View

Buckland P, ODonovan M, McGuffin P . Clozapine and sulpiride up-regulate dopamine D3 receptor mRNA levels. Neuropharmacology. 1993; 32(9):901-7. DOI: 10.1016/0028-3908(93)90146-t. View

Van Tol H, Bunzow J, Guan H, Sunahara R, Seeman P, Niznik H . Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991; 350(6319):610-4. DOI: 10.1038/350610a0. View

Jonsson E, Lannfelt L, Sokoloff P, Schwartz J, Sedvall G . Lack of association between schizophrenia and alleles in the dopamine D3 receptor gene. Acta Psychiatr Scand. 1993; 87(5):345-9. DOI: 10.1111/j.1600-0447.1993.tb03384.x. View

Nimgaonkar V, Zhang X, CALDWELL J, Ganguli R, Chakravarti A . Association study of schizophrenia with dopamine D3 receptor gene polymorphisms: probable effects of family history of schizophrenia?. Am J Med Genet. 1993; 48(4):214-7. DOI: 10.1002/ajmg.1320480408. View

Nothen M, Cichon S, Propping P, Fimmers R, Schwab S, Wildenauer D . Excess of homozygosity at the dopamine D3 receptor gene in schizophrenia not confirmed. J Med Genet. 1993; 30(8):708. PMC: 1016510. DOI: 10.1136/jmg.30.8.708. View

Laurent C, Savoye C, Samolyk D, Meloni R, Mallet J, Campion D . Homozygosity at the dopamine D3 receptor locus is not associated with schizophrenia. J Med Genet. 1994; 31(3):260. PMC: 1049763. DOI: 10.1136/jmg.31.3.260-a. View

10.

Yang L, Li T, Wiese C, Lannfelt L, Sokoloff P, Xu C . No association between schizophrenia and homozygosity at the D3 dopamine receptor gene. Am J Med Genet. 1993; 48(2):83-6. DOI: 10.1002/ajmg.1320480205. View

11.

Sokoloff P, Martres M, Giros B, Bouthenet M, Schwartz J . The third dopamine receptor (D3) as a novel target for antipsychotics. Biochem Pharmacol. 1992; 43(4):659-66. DOI: 10.1016/0006-2952(92)90227-a. View

12.

Seeman P . Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacology. 1992; 7(4):261-84. View

13.

Sokoloff P, Giros B, Martres M, Bouthenet M, Schwartz J . Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990; 347(6289):146-51. DOI: 10.1038/347146a0. View

14.

KOLAKOWSKA T, Williams A, Ardern M, Reveley M, Jambor K, Gelder M . Schizophrenia with good and poor outcome. I: Early clinical features, response to neuroleptics and signs of organic dysfunction. Br J Psychiatry. 1985; 146:229-39. DOI: 10.1192/bjp.146.3.229. View

15.

Nanko S, Sasaki T, Fukuda R, Hattori M, Dai X, KAZAMATSURI H . A study of the association between schizophrenia and the dopamine D3 receptor gene. Hum Genet. 1993; 92(4):336-8. DOI: 10.1007/BF01247330. View

16.

Meltzer H . Dimensions of outcome with clozapine. Br J Psychiatry Suppl. 1992; (17):46-53. View

17.

Mant R, Williams J, Asherson P, Parfitt E, McGuffin P, Owen M . Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia. Am J Med Genet. 1994; 54(1):21-6. DOI: 10.1002/ajmg.1320540106. View

18.

Shaikh S, Collier D, Kerwin R, Pilowsky L, Gill M, Xu W . Dopamine D4 receptor subtypes and response to clozapine. Lancet. 1993; 341(8837):116. DOI: 10.1016/0140-6736(93)92594-j. View

19.

Crocq M, Mant R, Asherson P, Williams J, Hode Y, MAYEROVA A . Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. J Med Genet. 1992; 29(12):858-60. PMC: 1016201. DOI: 10.1136/jmg.29.12.858. View

20.

Egger M, Smith G . Misleading meta-analysis. BMJ. 1995; 310(6982):752-4. PMC: 2549158. DOI: 10.1136/bmj.310.6982.752. View