Study of HLA-DRB1 genotyping in schizophrenia in Japanese

BIOI. PSYCHIATRY 1996:39:500-666

Abstrocls

140. B37 TRINUCLEOTIDE REPEATS IN SCHIZOPHRENIC PATIENTS AND FRENCH AND AFRICAN CONTROLS

DJ. Morris-Rosendahl I , E. Burgert l •2, J.P. Macher3 , A. Mayerova l , F. Duval 3 , & M.A. Crocq3 IInslitut mr Humangcl1l.!tik, 2rmaitUl rur Rechlsmedizin. FrI.!iburg University, 79106 Frelburg. Gemlany; ~Ccnlre Hospitalier. 63250 Roum.lch. France The llbnonnal expansion of lrinucleotide repeats in genl.!s is responsible for sevcrnl neurological disorders. It ha.~ been po5tul~lcd th:1l this phenomenon is also consislent with Ihe pallern of inherilance of major psychoses, where cases of ll.nticip:llion ha\le been reported. Expansion of a CAG rcpcil.t in the 837 gene on chromosome 12p is responsible for dentatorobrul-pallidoluysian atrophy (ORPLA). a ncurodegenerative dis· oruer that can mimic some symptoms of schizophrenia. Th<:refore. we in\lestigall.!d thll CAG rcpc:tts in the 837 gene in unrcl.lled Frencll schizophrenic inpalicnl~ (n=86) dingnoscrJ llccording 10 OSM-IV••md in French (n'=SO) ami Congolc!'e (n=32) conlrols. Gllnolyping was performed using the PeR and polyacrylamidll sci electrophoresis. A bimodal distribution of al h:les containing from 7 to 20 CAG rcpeats were obscrved in both schizophrenics and European controls; anti an aUele wilh 16 repeats wa... most common in bolh groups. Our resulls did nol reveal unusually long alleles in schizophrenic paticnls Ihm would susgesl o.bnoml:tl expansion of the CAG repeats. In facI, thl.!te was a non· significant (p=O.056) lrend lowards alleles with fewer repeats in schizophrenics as compared to European comrols. 'Illere was, however. a significant difference in heterozygosity between the schil.ophrcnic group (86%) as opposed to European (72%) llnd Congolese (72%) controls. In atconJanee with previous reports in Africllns. the Congolese controls hud significantly fewer repealS than the Europeans (p
141. STUDY OF HLA-DRBI GENOTYPING IN SCHIZOPHRENIA IN JAPANESE

T. Fujimoto 1, M. Sada2, T. Takano l K. Takeuchi I, K. Horinouchj, T. Tsuji 2 & H. Akimoto 3 ISouth Japllll H~a1th Science Center, Fujimoto Hospital. Miynkonojo 885 Japan: ~Resl:arch Institule National Cardiovascular Cenler: JMatsulawa Hospital Schizophrenia is helerogeneous in terms of eliology. Recent studies support lh:tt genelie fllctors may conlribule to Ihe clluse of schizophrenia. The DNA recombinant teclmology ha!'i made rcasilJlc the molecular analysis of the HLA class II genclic polymorphism, We performed gcnotyping aboul the first domain of lhe DR ~ehllin of schizophrenic palients to in\lcstigllte the rchltionship between ORB I gene nnd schizo. phrenia in Japanese. Ninety-eight sehiwphrenic patients (male 47. female 51 llnd mClIn Ilgc 47.6 :!: 11.8 yellrs.) WllTC sludied after infomu:d cunscnt. The ORB 1alleles of p:llients Were detected by m~lhods of peR (polymcClL'iC chain rCllction)·LIPA (line probe assay) and peR-SSP (sequence specific primers). The frequency of DR antigens lind ORB I nllcles in patients were complIrcdto lhose of healthy Jap:tncsc conlrol

541

(DR amigens of 898 and ORB J nllllIeli of 493. 11th International HLA

Workshop 1991), The frequencies of DR antigens in pati1:ln[s .....ere significantly elevmeti in DRI4 (GF""9.7. P"'O.0234. RR=I.9). DR9 (18,6, P significantly higher in DRBI·0406 (7.7) [han lhal of the conlrol (3.5) (P=O,OO58. RR=2.4). The frequency in palients Was also significantly higher in ORB 1·0901 (18.4) lhan the control (13.7) (P=0.023S. RR= 17), The DR nnligen homo \V:tli n=4 (29%) in DR4, 0'=4 (29%) in DRS. n=3 (21%) in DR9 and 1'1=3 (21 %) in DRI5, 111cse results suggesled an a.~soci::ttion between lhe DRBI gene and schizophrenia in Japanese. HLA·ORBI genolyping is a useful 111~thod Cor genclie analysis of schizophrenia,

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142. ANALYSIS OF HLA-DRBI ALLELES IN ALCOHOLISM IN JAPANESE T. Fujimoto 1, M. Sada 2, T. Uchida l , T. Nakano I, T. Tsuji 2 & H. Akimoto3 ISouth Japan Hcallh Science Cenler. Daiso Hospital. Mimala 885-19 Japan; 2Research In!'litutc Nmion:tl Canliovllscular Center: ~Matsuzawa Hospiml Since alcoholism is a clinically helerogeneolls condition, genetic flleton; may be imponllnl in the pmhogenesis of alcoholism. Human leukocyte antigen (HlA) is a genetic factor which delennines susceptibilily. rllsislance and individual difference in diseases with unknown eliology.1t wal: reported lhat there was a correlation bl!tween polymorphism or HLA molecule and Yllrious Llise:tses, including alcoholism, using the serological mel hod. Rccent advances of the polymcl".lse chain rellclion (peR) method made it feasiblc to define more corr~ctly DR anligen tban the moloBicnl method. fllA·ORBl gcnotyping WllS performed using the PeR·line probe assay (PCR-LIPA) and PeR-sequence llpccilie primers (PCR·SSP) melhod!'. The ULA-DRB I llluuy was conducted on 43 :Ilcoholics (male, mean ugc of 50, 2:!: 7. tl )lears) who were inp~ticnts in :l hospil~l for lllcoholism, Frequencies of DR antigen and ORB I allelcs in patienls were compared 10 those of heallhy Japanese conlrol, Resulls of sludles in DR antigen of 898 Jllpullllse healthy subjccls and DRB I alleles of 493 were used us controls (lIlh International .ILA Workshop 1991). The frequencies or DR nntigen in alcoholics were significantly increased in DR 10 (P=O. 0601. RR=3. 9) and DR blank(bk) (P
143. AUTISM AND THE X-CHROMOSOME: MULTIPOINT SIB PAIR ANALYSIS

J. Hallmayer, J. Heberl. D. Spiker, L. Lotspeich, W.M. McMahon, P.B.Petersen, P. Nicholas, C. Pingree, A. Lin, N. Risch, L. Cavalli-Sforza, & R.D. Ciaranello Dept. of Psychiatry & Behavioral Sciences, lind Dept. of Genetics. Sianrord University. Mllil Code 5540, Stanford. CA 94305 Genetic fDctors undoubledly play .lI major eliologie role in autism, but how it is inherited rem:lins unan.~wercd. Thc increas~d incidence in males