Association analysis of the HOPA12bp polymorphism in schizophrenia and manic depressive illness.
Variations in exon 42 of the HOPA (human opposite paired) gene have been associated with mental retardation, hypothyroidism and psychiatric disorders. We attempted to replicate the association with schizophrenia using 309 parent-offspring trios from Bulgaria and 367 unrelated cases and 368 blood donors from the UK. We also tested 125 bipolar trios from Bulgaria, 112 bipolar trios from the UK and a sample of 178 unrelated bipolar cases and 188 blood donors from the UK. The frequency of HOPA(12bp) in the 556 UK blood donors was 2.6% and it was not significantly different in the UK patients groups, where it ranged from 1.2 to 3.8%. Sixteen mothers transmitted the HOPA(12bp) allele to schizophrenic offspring, while 12 did not transmit, a non-significant difference. There was a trend for under-transmission of the rare allele to bipolar patients (T/NT = 4/10) and they had a lower rate of that allele than schizophrenic patients in the Bulgarian population (1% vs. 4.2%, P = 0.043). However the two diagnostic groups had similar allele frequencies in the UK populations: 2% versus 2.6%, P = 0.6. We conclude that the HOPA polymorphism is unlikely to be a major risk factor in the pathogenesis of these major psychiatric disorders although there could be a small effect in schizophrenia.
Kirov
George
G
Neuropsychiatric Genetics Unit, Department of Psychological Medicine, University of Wales College of Medicine, Tenovus Building, Heath Park, Cardiff CF144 4XN, Wales, UK. kirov@cardiff.ac.uk
Georgieva
Ludmila
L
Nikolov
Ivan
I
Zammit
Stan
S
Jones
Gaynor
G
Poriazova
Nadezhda
N
Tolev
Todor
T
Owen
Richard
R
Jones
Sue
S
Owen
Michael J
MJ
D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002031:Bulgaria; D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D056892:Mediator Complex; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D006113:United Kingdom
C460107:MED12 protein, human; D056892:Mediator Complex; D011988:Receptors, Thyroid Hormone