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Functional polymorphism ( C ‐ 824T ) of the tyrosine hydroxylase gene affects IQ in schizophrenia
Author(s) -
Horiguchi Mieko,
Ohi Kazutaka,
Hashimoto Ryota,
Hao Qinyu,
Yasuda Yuka,
Yamamori Hidenaga,
Fujimoto Michiko,
UmedaYano Satomi,
Takeda Masatoshi,
Ichinose Hiroshi
Publication year - 2014
Publication title -
psychiatry and clinical neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 74
eISSN - 1440-1819
pISSN - 1323-1316
DOI - 10.1111/pcn.12157
Subject(s) - tyrosine hydroxylase , allele , genotype , reporter gene , schizophrenia (object oriented programming) , dopamine , gene , promoter , biology , single nucleotide polymorphism , genetics , microbiology and biotechnology , gene expression , endocrinology , psychology , psychiatry
Aims Progressive cognitive decline has been an important issue in the treatment and care of patients with schizophrenia. Tyrosine hydroxylase ( TH ) is the rate‐limiting enzyme for the biosynthesis of catecholamine, including dopamine and noradrenaline. In this report, we examined a possible association of a genetic variant in the TH promoter region. Methods Association of a genetic variant in the TH promoter region, C ‐824T (rs10770141), with intellectual ability in 132 patients with schizophrenia and 282 healthy subjects was examined. The transcriptional activity of the plasmids harboring the TH promoter region with either C or T nucleotide at −824 was assayed using a luciferase gene as a reporter. Results We found significant effects of the genotype on the full‐scale IQ , verbal IQ , and performance IQ , in patients with schizophrenia. IQ was lower in individuals with the C / C genotype than those with T carriers. The plasmid with the T allele at −824 showed higher transcriptional activity than that with the C allele in a transient transfection experiment using a luciferase gene as a reporter, implying that the T carriers may have higher TH activities and retain higher levels of catecholamines in the brain. Conclusions The present data suggest that the biosynthesis of catecholamine by the action of TH should be deeply involved in decreased intellectual ability in patients with schizophrenia. This is the first report, as far as we know, showing a correlation between TH expression and IQ in humans.