WATANABE Akiko Tokyo Medical and Dental University, Department of Neuropsychiatry, Research Assistant, 医学部, 技官(教務職員) (40210992)
SHIBUYA Haruo National Sanatorium Minami-Hanamaki Hospital, Director, 南花巻病院, 院長 (10158959)
KURUMAJI Akeo Tokyo Medical and Dental University, Department of Neuropsychiatry, Lecturer, 医学部, 講師 (00251504)
|Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
In our search for candidate genes for affective disorder on the short arm of chromosome 18, we cloned IMPA2, a previously unreported myo-inositol monophosphatase, that mapped to 18p11.2. Recently, a marker GOLF was shown to be linked to schizophrenia by both linkage analysis and family-based association study. Interestingly the location of the IMPA2 is very close to the GOLF(100kb). For the screening of mutations in the IMPA2 gene, we have determined the genomic structure and identified 10 different polymorphisms: (1)-466G>A (promoter), (2)-219C>T (promoter), (3)58G>A (exon 1), (4)IVS1-15G>A, (5)401T>C (Leu53Leu) (exon 2), (6)468C>T (His76tyr) (exon 2), (7)IVS5+13-14insA (intron 5), (8)776T>C (Arg178Arg), (9)800C>T (Phe186Phe) (exon6), (10)1079C>G (Thr279Thr) (exon 8). In the present study, we performed association tests on Japanese cohorts that included 302 schizophrenics, 212 patients with affective disorder and 308 matched controls. The missense mutation (His76Tyr) was not detected in these samples. We genotyped the three different polymorphisms, (3), (4) and (9). None of these were found to be associated with mood disorders. In contrast, in the schizophrenia sample there were significant genotypic and/or allelic associations regarding all the polymorphisms. These results suggest that the IMPA2 gene may be involved in a pathogenesis of schizophrenia in Japanese population. Since possible functional polymorphisms are only those which exist in the promoter region, it will be important to examine transcriptional consequences induced by those variants, in addition to refine the critical region by further genetic analysis.