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Association of schizophrenia in African Americans to polymorphism in synapsin III gene

Lachman, Herbert M.a; Stopkova, Pavlab; Rafael, Maryam Aghalara; Saito, Takuyaa

ORIGINAL ARTICLES

Linkage studies in families with schizophrenia have pointed to chromosome 22q12–q13 as one of several regions of the genome that may contain a susceptibility gene. The gene coding for synapsin III, an intrinsic synaptic vesicle membrane protein, maps to this target region. Two tightly linked single-nucleotide polymorphisms were recently found in a small subset of patients with SZ – a synonymous variant, L469L (469G>A), and a non-synonymous variant, S470N (470G>A) – which results in the loss of a mitogen-activated protein kinase serine phosphorylation site. We also found a slight increase in 470A in Caucasian patients from the US with schizophrenia. But, the sample size and allele frequency were too small to draw definitive conclusions. However, both single-nucleotide polymorphisms were much more polymorphic in African American controls than in Caucasian controls, thereby providing a better sample cohort to analyze for schizophrenia involvement. For the codon 469 single-nucleotide polymorphisms, a 50-fold increase was observed in the frequency of 469A in African Americans compared with Caucasians. Furthermore, there was an increase in the percentage of African American patients with schizophrenia who were homozygous for the 469A allele compared with controls who were homozygous (11 versus 5%; AA vs. all other genotypes – Fisher statistic=3.08, P=0.04, one-tailed). An increase in 470A heterozygotes was also found, but the results fell short of being statistically significant. The findings support a role for synapsin III in a subset of African American patients with schizophrenia and raises questions about selective pressure in Africa to account for the extraordinary disparity of the 469 and 470 single-nucleotide polymorphisms in different ethnic populations.

aDepartment of Psychiatry and Behavioral Sciences, Division of Psychiatry Research, Albert Einstein College of Medicine, Bronx, New York, USA

bPsychiatric Clinic, First Medical Faculty, Charles University, Prague, Czech Republic

Sponsorship: Funding for this project was from an Independent Investigator Award from NARSAD (H.M.L).

Correspondence and requests for reprints to H. M. Lachman, Albert Einstein College of Medicine1300 Morris Park Avenue, Bronx, NY 10461, USA

Tel: 718 430 2428; fax: 718-430-8772;

e-mail: Lachman@aecom.yu.edu

Accepted 13 October 2004

© 2005 Lippincott Williams & Wilkins, Inc.