Study of genetic markers on the short arm of the chromosome 6 (6p) in schizophrenia : analysis of schizophrenia susceptibility gene

我们获得的结果表明，在两个独立的患者群体中，位于6号染色体短臂的HLA基因座与精神分裂症之间存在关联。这一结果与日本以往的小型研究一致，有力地表明，到1998年度末，日本精神分裂症患者的HLA-DR 1频率增加（Am J Psychiatry 56 ; 771-773，1999）。我们研究了另一组精神分裂症患者和对照组的HLA-DR 1和DR 4频率。在精神分裂症患者中观察到具有DR 1的受试者增加（p < 0.05），与先前的结果一致。本研究通过对精神分裂症患者的临床和人口统计学变量与DR 1的关系的研究，探讨HLA在精神分裂症发病中的可能作用机制。在精神分裂症患者中，观察到冬季出生（2月至3月）与DR 1之间的显著关联（p < 0.005）。这表明与冬季分娩有关的因素（如产前或围产期流感感染和寒冷天气的影响）可能与HLA相互作用并影响精神分裂症的后期发展（Am J Psychiatry，出版中）。

We had obtained a result to indicate an association between the HLA locus, located at the short arm of the chromosome 6, and schizophrenia in two independent patient groups. The result was consistent with previous small Japanese studies, strongly suggesting an increase of HLA-DR1 frequency in Japanese patients with schizophrenia by the end of fiscal 1998 (Am J Psychiatry 56 ; 771-773, 1999).In fiscal 1999, we further investigated the issue to confirm this result. We studied HLA-DR1 and DR4 frequencies in another group of schizophrenia patients and control subjects. An increase of subjects possessing DR1 in schizophrenia patients was observed (p < 0.05), consistent with the previous results. No difference of DR4 frequency was observed between the patients and controls, thus we failed to confirm a decrease of DR4 frequency in schizophrenia, which was reported in Caucasian studies (Schizophrenia Res, in press).Also, we investigated relationship between clinical and demographic variables and DR1 in schizophrenia, to study a possible mechanism of a role of HLA in schizophrenia. A significant association between winter birth (February-March) and DR1 was observed in schizophrenia patients (p < 0.005). This suggests that a factor related to winter birth (such as an effect of influenza infection and cold weather during the pre or peri-ntal period) might interact with HLA and influence the later development of schizophrenia (Am J Psychiatry, in press).