Hyperprolinemia is a risk factor for schizoaffective disorder
Hyperprolinemia is a risk factor for schizoaffective disorder
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DOI：
10.1038/sj.mp.4001597
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发表时间：
2005-05-01
影响因子：
11
通讯作者：
Campion, D
中科院分区：
文献类型：
--
作者：
Jacquet, H;Demily, C;Campion, D
22 q11 DiGeorge染色体区域内的DNA序列变异可能会导致精神病的易感性。在以前的报告中，我们确定了几个杂合的改变，包括一个完整的缺失，脯氨酸脱氢酶（PRODH）基因，这与中度高脯氨酸血症的DSM III精神分裂症患者的一个子集。我们的目的是（i）确定高脯氨酸血症是否与三种精神疾病（精神分裂症、情感障碍和双相情感障碍）的易感性增加有关;（ii）建立高脯氨酸血症与PRODH基因型之间的相关性。我们进行了一项病例对照研究，包括114名对照者，188名精神分裂症患者，63名双情感障碍患者和69名双相情感障碍患者。我们报告，考虑到丙戊酸盐治疗的混杂效应，高脯氨酸血症是DSM IIIR情感障碍的风险因素（P = 0.02，比值比= 4.6，95%置信区间1.3 - 16.3）。我们没有检测到22q11间质性缺失与DiGeorge综合征在我们的样本中的320例患者，我们发现常见的PRODH多态性和任何精神疾病之间没有关联。相比之下，我们发现五个罕见的PRODH改变（包括一个完整的PRODH缺失和四个错义取代）与高脯氨酸血症。在一些情况下，两种变异同时存在，无论是顺式或反式在同一主题。30例高脯氨酸血症受试者中共有11例至少存在一种与高脯氨酸血症相关的遗传变异。这项研究表明，中度高脯氨酸血症是一个中间表型与某些形式的精神病。
DNA sequence variations within the 22q11 DiGeorge chromosomal region are likely to confer susceptibility to psychotic disorders. In a previous report, we identified several heterozygous alterations, including a complete deletion, of the proline dehydrogenase (PRODH) gene, which were associated with moderate hyperprolinemia in a subset of DSM III schizophrenic patients. Our objective was (i) to determine whether hyperprolinemia is associated with increased susceptibility for any of three psychiatric conditions (schizophrenia, schizoaffective disorder and bipolar disorder) and (ii) to establish a correlation between hyperprolinemia and PRODH genotypes. We have conducted a case-control study including 114 control subjects, 188 patients with schizophrenia, 63 with schizoaffective disorder and 69 with bipolar disorder. We report that, taking into account a confounding effect due to valproate treatment, hyperprolinemia is a risk factor for DSM IIIR schizoaffective disorder (P = 0.02, Odds ratio = 4.6, 95% confidence interval 1.3-16.3). We did not detect 22q11 interstitial deletions associated with the DiGeorge syndrome among the 320 patients of our sample and we found no association between common PRODH polymorphisms and any of the psychotic disorders. In contrast, we found that five rare PRODH alterations (including a complete PRODH deletion and four missense substitutions) were associated with hyperprolinemia. In several cases, two variations were present simultaneously, either in cis or trans in the same subject. A total of 11 from 30 hyperprolinemic subjects bore at least one genetic variation associated with hyperprolinemia. This study demonstrates that moderate hyperprolinemia is an intermediate phenotype associated with certain forms of psychosis.