Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volumn 39, Issue 1, 2012, Pages 163-169

  Wright, Galen E B ^a   Niehaus, Dana J H ^a   van der Merwe, Lize ^b,c   Koen, Liezl ^a   Korkie, Lundi J ^a   Kinnear, Craig J ^a   Drögemöller, Britt I ^a   Warnich, Louise ^a  

^a STELLENBOSCH UNIVERSITY   (South Africa)

^b SOUTH AFRICAN MEDICAL RESEARCH COUNCIL   (South Africa)

^c UNIVERSITY OF THE WESTERN CAPE   (South Africa)

Author keywords

African population; MB COMT; Negative symptoms; Schizophrenia; Xhosa

Indexed keywords

CATECHOL METHYLTRANSFERASE;

ADULT; ALLELE; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; FEMALE; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HAPLOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; MB COMT GENE; NEGATIVE SYNDROME; NEGRO; PROMOTER REGION; REPORTER GENE; SCHIZOPHRENIA; SCORING SYSTEM; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; AFRICAN CONTINENTAL ANCESTRY GROUP; ALLELES; CASE-CONTROL STUDIES; CATECHOL O-METHYLTRANSFERASE; CELL LINE; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HAPLOTYPES; HUMANS; ISOENZYMES; MALE; MEMBRANE PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; PSYCHIATRIC STATUS RATING SCALES; SCHIZOPHRENIA; SYMPTOM ASSESSMENT;

EID: 84864521575     PISSN: 02785846     EISSN: 18784216     Source Type: Journal    
DOI: 10.1016/j.pnpbp.2012.06.006     Document Type: Article

References (42)

1. Achim A.M., Maziade M., Raymond E., Olivier D., Mérette C., Roy M.A. How prevalent are anxiety disorders in schizophrenia? A meta-analysis and critical review on a significant association. Schizophr Bull 2011, 37:811-821.
2. Andreasen N.C. The scale for the assessment of negative symptoms (SANS) 1983, University of Iowa, Iowa City.
3. Andreasen N.C. The scale for the assessment of positive symptoms (SAPS) 1984, University of Iowa, Iowa City.
4. Badner J.A., Gershon E.S. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002, 7:405-411.
5. Barrett J.C., Fry B., Maller J., Daly M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265.
6. Bray N.J., Buckland P.R., Williams N.M., Williams H.J., Norton N., Owen M.J., et al. A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Am J Hum Genet 2003, 73:152-161.
7. Chen J., Lipska B.K., Halim N., Ma Q.D., Matsumoto M., Melhem S., et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 2004, 75:807-821.
8. Chen X., Wang X., O'Neill A.F., Walsh D., Kendler K.S. Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. Mol Psychiatry 2004, 9:962-967.
9. Guillin O., Abi-Dargham A., Laruelle M. Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol 2007, 78:1-39.
10. Ji Y., Olson J., Zhang J., Hildebrandt M., Wang L., Ingle J., et al. Breast cancer risk reduction and membrane-bound catechol O-methyltransferase genetic polymorphisms. Cancer Res 2008, 68:5997-6005.
11. Kety S.S. The significance of genetic factors in the etiology of schizophrenia: results from the national study of adoptees in Denmark. J Psychiatr Res 1987, 21:423-429.
12. Kobrynski L.J., Sullivan K.E. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 2007, 370:1443-1452.
13. Koen L., Jonathan R., Niehaus D.J. Cannabis use and abuse correlates in a homogeneous South African schizophrenia population. S Afr J Psychiatry 2009, 15:8-12.
14. Lachman H.M., Papolos D.F., Saito T., Yu Y.M., Szumlanski C.L., Weinshilboum R.M. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996, 6:243-250.
15. Li W.J., Kou C.G., Yu Y., Sun S., Zhang X., Kosten T.R., et al. Association of catechol-O-methyltransferase gene polymorphisms with schizophrenia and negative symptoms in a Chinese population. Am J Med Genet B Neuropsychiatr Genet 2012, 159B:370-375.
16. Lin P.I., Vance J.M., Pericak-Vance M.A., Martin E.R. No gene is an island: the flip-flop phenomenon. Am J Hum Genet 2007, 80:531-538.
17. Manolio T.A., Collins F.S., Cox N.J., Goldstein D.B., Hindorff L.A., Hunter D.J., et al. Finding the missing heritability of complex diseases. Nature 2009, 461:747-753.
18. Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988, 16:1215.
19. Mukherjee N., Kidd K.K., Pakstis A.J., Speed W.C., Li H., Tarnok Z., et al. The complex global pattern of genetic variation and linkage disequilibrium at catechol-O-methyltransferase. Mol Psychiatry 2010, 15:216-225.
20. Nackley A.G., Shabalina S.A., Tchivileva I.E., Satterfield K., Korchynskyi O., Makarov S.S., et al. Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 2006, 314:1930-1933.
21. Niculescu A.B., Le-Niculescu H. The P-value illusion: how to improve (psychiatric) genetic studies. Am J Med Genet B Neuropsychiatr Genet 2010, 153B:847-849.
22. Niehaus D.J., Koen L., Laurent C., Muller J., Deleuze J.F., Mallet J., et al. Positive and negative symptoms in affected sib pairs with schizophrenia: implications for genetic studies in an African Xhosa sample. Schizophr Res 2005, 79:239-249.
23. Niehaus D.J., Koen L., Muller J., Laurent C., Stein D.J., Lochner C., et al. Obsessive compulsive disorder-prevalence in Xhosa-speaking schizophrenia patients. S Afr Med J 2005, 95:120-122.
24. Niehaus D.J., du Plessis S.A., Koen L., Lategan B.H., Steyn J., Oosthuizen P.P., et al. Predictors of abnormal involuntary movement in an African schizophrenia population. J Neuropsychiatry Clin Neurosci 2008, 20:317-326.
25. Nyholt D.R. A simple correction for multiple testing for single nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 2004, 74:765-769.
26. Okochi T., Ikeda M., Kishi T., Kawashima K., Kinoshita Y., Kitajima T., et al. Meta-analysis of association between genetic variants in COMT and schizophrenia: an update. Schizophr Res 2009, 110:140-148.
27. Perneger T.V. What's wrong with Bonferroni adjustments. BMJ 1998, 316:1236-1238.
28. Pooley E.C., Fineberg N., Harrison P.J. The met(158) allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psychiatry 2007, 12:556-561.
29. Roffman J.L., Brohawn D.G., Nitenson A.Z., Macklin E.A., Smoller J.W., Goff D.C. Genetic variation throughout the folate metabolic pathway influences negative symptom severity in schizophrenia. Schizophr Bull 2011, 10.1093/schbul/sbr150.
30. Shifman S., Bronstein M., Sternfeld M., Pisanté-Shalom A., Lev-Lehman E., Weizman A., et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002, 71:1296-1302.
31. Tenhunen J., Salminen M., Lundström K., Kiviluoto T., Savolainen R., Ulmanen I. Genomic organization of the human catechol O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem 1994, 223:1049-1059.
32. Tishkoff S.A., Reed F.A., Friedlaender F.R., Ehret C., Ranciaro A., Froment A., et al. The genetic structure and history of Africans and African Americans. Science 2009, 324:1035-1044.
33. Van Os J., Kapur S. Schizophrenia. Lancet 2009, 374:635-645.
34. Wang Y., Fang Y., Shen Y., Xu Q. Analysis of association between the catechol-O-methyltransferase (COMT) gene and negative symptoms in chronic schizophrenia. Psychiatry Res 2010, 179:147-150.
35. Williams H.J., Owen M.J., O'Donovan M.C. Is COMT a susceptibility gene for schizophrenia?. Schizophr Bull 2007, 33:635-641.
36. Wright G.E., Niehaus D.J., Koen L., Drögemöller B.I., Warnich L. Psychiatric genetics in South Africa: cutting a rough diamond. Afr J Psychiatry (Johannesbg) 2011, 14:355-366.
37. Xie T., Ho S.L., Ramsden D. Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. Mol Pharmacol 1999, 56:31-38.
38. Gregory Warnes, with contributions from Gregor Gorjanc, Friedrich Leisch and Michael Man. genetics: Population Genetics. R package version 1.3.6. (Available at:) [Accessed: 23 April 2012], 2011. http://CRAN.R-project.org/package=genetics.
39. Sinnwell J.P., Schaid D.J. haplo.stats: statistical analysis of haplotypes with traits and covariates when linkage phase is ambiguous. R package version 1.5.5 Available at:, [Accessed: 23 April 2012]. http://CRAN.R-project.org/package=haplo.stats.
40. The R Project for Statistical Computing Available at:, [Accessed: 23 April 2012]. http://www.r-project.org.
41. Statistics South Africa: census 2001 Available at:, [Accessed: 23 April 2012]. http://www.statsonline.gov.za/census01/html/RSAPrimary.pdf.
42. SZGene (SchizophreniaGene) database: meta-analysis of all published SZ association studies (case-control only) rs737865 Available at:, [Accessed: 23 April 2012]. http://www.szgene.org/meta.asp?geneID=420.