Human Genetics

, Volume 116, Issue 4, pp 319–328

Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans

  • Seong-Gene Lee
  • Yeonho Joo
  • Byungsu Kim
  • Seockhoon Chung
  • Hie-Lim Kim
  • Inchul Lee
  • Boyoul Choi
  • Changyoon Kim
  • Kyuyoung Song
Original Investigation

DOI: 10.1007/s00439-004-1239-y

Cite this article as:
Lee, SG., Joo, Y., Kim, B. et al. Hum Genet (2005) 116: 319. doi:10.1007/s00439-004-1239-y

Abstract

Catechol-O-methyltransferase (COMT) inactivates circulating catechol hormones, catechol neurotransmitters, and xenobiotic catecholamines by methylating their catechol moieties. The COMT gene has been suggested as a candidate gene for schizophrenia through linkage analyses and molecular studies of velo-cardio-facial syndrome. A coding polymorphism of the COMT gene at codon 108/158 (soluble/membrane-bound form) causing a valine to methionine substitution has been shown to influence enzyme activity, but its association with schizophrenia is inconclusive. We have screened 17 known polymorphisms of the COMT gene in 320 Korean schizophrenic patients and 379 controls to determine whether there is a positive association with a nonsynonymous single-nucleotide polymorphism (rs6267) at codon 22/72 (soluble/membrane-bound form) causing an alanine-to-serine (Ala/Ser) substitution. With the Ala/Ala genotype as a reference group, the combined genotype (Ala/Ser and Ser/Ser)-specific adjusted odds ratio was 1.82 (95% CI=1.19–2.76; P=0.005), suggesting the Ser allele as a risk allele for schizophrenia. However, the Val/Met polymorphism was not associated with an increased risk of schizophrenia in Koreans (OR=0.88, 95% CI=0.64–1.21; P=0.43). The Ala72Ser substitution was correlated with reduced COMT enzyme activity. Our results support previous reports that the COMT haplotype implicated in schizophrenia is associated with low COMT expression.

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Seong-Gene Lee
    • 1
    • 2
  • Yeonho Joo
    • 3
  • Byungsu Kim
    • 3
  • Seockhoon Chung
    • 3
  • Hie-Lim Kim
    • 4
  • Inchul Lee
    • 5
  • Boyoul Choi
    • 6
  • Changyoon Kim
    • 3
  • Kyuyoung Song
    • 4
  1. 1.Asan Institute for Life SciencesUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of Biotechnology, College of Agriculture and Life SciencesChonnam National UniversityGwangjuKorea
  3. 3.Department of PsychiatryUniversity of Ulsan College of MedicineSeoulKorea
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of PathologyUniversity of Ulsan College of MedicineSeoulKorea
  6. 6.Department of Preventive Medicine, College of MedicineHanyang UniversitySeoulKorea

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