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Analysis of variations in the NAPG gene on chromosome 18p11 in bipolar disorder

Weller, Andrew E.; Dahl, John P.; Lohoff, Falk W.; Ferraro, Thomas N.; Berrettini, Wade H.

doi: 10.1097/01.ypg.0000180678.88169.b0
ORIGINAL ARTICLES

Objective A number of studies have implicated the chromosome 18p11 region as a susceptibility region for bipolar disorder. The gene encoding γ-SNAP (NAPG), one of three soluble N-ethylmaleimide-sensitive fusion (NSF)-attachment proteins (SNAPs), is located in the 18p11 region and is thought to play a role in cellular processes required for neurotransmission in the central nervous system. The purpose of this study is to investigate whether polymorphisms in the human NAPG gene contribute to the etiology of bipolar disorder.

Methods To test this hypothesis, we used a case–control design in which the genotype and allele frequencies for five single-nucleotide polymorphisms in the human NAPG gene were compared between individuals with a diagnosis of type I bipolar disorder (n=460) and control individuals (n=191).

Results The genotype results indicate that three of the single-nucleotide polymorphisms in the NAPG gene, rs2290279 (P=0.027), rs495484 (P=0.044) and rs510110 (P=0.046), show a nominal, statistically significant association with bipolar disorder at the genotype frequency level.

Conclusions The results of this study suggest that polymorphisms in the human NAPG gene may represent risk factors for the development of bipolar disorder, but before such a role can be established, the results of this study must be confirmed in additional populations of bipolar disorder patients and controls.

Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Correspondence and requests for reprints to John P. Dahl, 135b Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA

Tel: +215 573 4588; fax: +215 573 2041; e-mail: jdahl@mail.med.upenn.edu

Sponsorship: This work was supported by NIH grants R01 MH63876 and R01 MH 59553 to W.H.B, a NARSAD Distinguished Investigator Award to W.H.B as well as a grant from the Tzadekah Foundation to W.H.B.

Received 14 April 2005 Accepted 4 August 2005

© 2006 Lippincott Williams & Wilkins, Inc.