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

Herbert M. Lachman, Pavla Stopkova, Maryam Aghalar Rafael, Takuya Saito

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)127-132
Number of pages6
JournalPsychiatric Genetics
Volume15
Issue number2
DOIs
StatePublished - Jun 2005

Fingerprint

Synapsins
African Americans
Schizophrenia
Single Nucleotide Polymorphism
Genes
Synaptic Membranes
Synaptic Vesicles
Heterozygote
Mitogen-Activated Protein Kinases
Gene Frequency
Codon
Sample Size
Serine
Membrane Proteins
Cohort Studies
Chromosomes
Alleles
Genotype
Phosphorylation
Genome

Keywords

  • 22q12-q13
  • Bipolar disorder
  • Chromosome 22
  • Mitogen-activated protein kinase
  • S470N
  • Synaptic vesicle

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Neuroscience(all)

Cite this

Association of schizophrenia in African Americans to polymorphism in synapsin III gene. / Lachman, Herbert M.; Stopkova, Pavla; Rafael, Maryam Aghalar; Saito, Takuya.

In: Psychiatric Genetics, Vol. 15, No. 2, 06.2005, p. 127-132.

Research output: Contribution to journalArticle

Lachman, Herbert M. ; Stopkova, Pavla ; Rafael, Maryam Aghalar ; Saito, Takuya. / Association of schizophrenia in African Americans to polymorphism in synapsin III gene. In: Psychiatric Genetics. 2005 ; Vol. 15, No. 2. pp. 127-132.
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