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Lack of association between dopamine-β hydroxylase gene and a history of suicide attempt in schizophrenia: comparison of molecular and statistical haplotype analyses

Howe, Aaron S.a; Leung, Tiffanya; Bani-Fatemi, Alia; Souza, Renanc; Tampakeras, Mariab; Zai, Clementb; Kennedy, James L.b; Strauss, Johnb; De Luca, Vincenzoa

doi: 10.1097/YPG.0000000000000031
Original Articles

Objective(s): In the present study, we examined whether there was an association between dopamine-β hydroxylase (DBH) promoter polymorphisms (a 5′-ins/del and a GTn repeats) and a history of suicide attempt in 223 chronic schizophrenia individuals using statistical and molecular analyses. Within the genetic association study design, we compared the statistical haplotype phase with the molecular phase produced by the amplicon size analysis.

Materials and methods: The two DBH polymorphisms were analysed using the Applied Biosystem 3130 and the statistical analyses were carried out using UNPHASED v.3.1.5 and PHASE v.2.1.1 to determine the haplotype frequencies and infer the phase in each patient. Then, DBH polymorphisms were incorporated into the Haploscore analysis to test the association with a history of suicide attempt.

Results: In our sample, 62 individuals had a history of suicide attempt. There was no association between DBH polymorphisms and a history of suicide attempt across the different analytical strategies applied. There was no significant difference between the haplotype frequencies produced by the amplicon size analysis and statistical analytical strategies. However, some of the haplotype pairs inferred in the PHASE analysis were inconsistent with the molecular haplotype size measured by the ABI 3130.

Conclusion: The amplicon size analysis proved to be the most accurate method using the haplotype as a possible genetic marker for future testing. Although the results were not significant, further molecular analyses of the DBH gene and other candidate genes can clarify the utility of the molecular phase in psychiatric genetics and personalized medicine.

aGroup for Suicide Studies, CAMH

bNeurogenetics, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

cDepartment of General Biology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

Correspondence to Vincenzo De Luca, MD, PhD, Group for Suicide Studies, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College St, Toronto, ON, Canada M5T 1R8 Tel: +1 416 535 8501 x34421; fax: +1 416 979 4666; e-mail: vincenzo_deluca@camh.ca

Received April 18, 2013

Accepted February 24, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins