Neuregulin 1基因與精神分裂症之家族關聯研究: 遺傳負荷與精神病性症狀之影響
A Family-Based Association Study of Neuregulin 1 Gene and Schizophrenia: Influence of Genetic Loading and Psychotic Symptoms
Date Issued
2007
Date
2007
Author(s)
Huang, Shu-Ting
DOI
en-US
Abstract
目的：探討Neuregulin 1基因(NRG1)與精神分裂症家庭中不同的遺傳負荷之間的關係；同時利用家族關聯性分析去探究NRG1基因是否特別與精神分裂症之活性症狀有關。
方法：此研究的樣本可分為兩組：162個單發家庭(包含162個精神分裂症病患與355個一等親家屬)與42個多發家庭(包含83個精神分裂症病患與86個一等親家屬)，所有參加研究的個案均由受過訓練訪員進行遺傳診斷問卷(DIGS)的訪談與抽血。在遺傳診斷問卷中，利用活性症狀量表(SAPS)來評估精神症狀，另外，利用MALDI-TOF質譜分析法或ABI7900來進行NRG1上的六個單一核苷酸多形性(SNP)的鑑定，並採用FBAT軟體來進行家族資料之單一基因座與半形關聯性分析。
結果：在半形分析部分，發現rs3924999-rs2954041雙基因半形與SNP8NRG243177-rs3924999-rs2954041三基因半形僅在單發家庭樣本中呈現較不傳遞的現象。另外，在依活性症狀分層後，相似的結果也可以在妄想症狀的單發家庭中看到，在任一妄想或幻覺症狀方面，也可以看到此關係。
結論： NRG1與精神分裂症的關聯性特別在有妄想症狀和有無併發幻覺症狀之病患的單發家庭中發現。我們推論NRG1在較易受環境影響之精神分裂症偶發家庭中扮演著重要的角色，並導致妄想症狀的發展。
Objective. To examine the association between Neuregulin 1(NRG1) gene and schizophrenia in families of different genetic loading of schizophrenia and whether the association of the NRG1 gene is particularly with the positive symptoms of schizophrenia by means of family-based association analyses.
Methods. The subjects were from two different groups: 162 simplex families (162 schizophrenic probands and 355 of their first-degree relatives) and 42 multiplex families (83 schizophrenic probands and 86 of their first-degree relatives). All participants were interviewed by trained research assistants who used the Diagnostic Interview for Genetic Studies (DIGS), and drawn for peripheral blood. The DIGS also assessed psychopathological dimensions with the Scales for the Assessment of Positive Symptoms (SAPS). Six SNPs of the NRG1 gene were genotyped and FBAT program was used to perform single-locus and haplotype association analyses in family-based study
Results. The two-locus rs3924999-rs2954041 haplotype and the three-locus SNP8NRG243177-rs3924999-rs2954041 haplotype of NRG1were found to have a decreased transmission in the simplex families only, not in the multiplex ones. After stratification by positive symptoms of schizophrenia, similar results were found only for the simplex families of schizophrenia patients with delusion as well as for those with delusion or hallucination.
Conclusions. The association of NRG1 gene with schizophrenia is mainly limited to patients from simplex families having delusion with or without hallucination. We concluded that NRG1 gene may play a vital role in the sporadic form of schizophrenia that is more vulnerable to environmental influences and leads to the development of delusion.
Subjects
家族關聯性
Neuregulin 1
精神分裂症
遺傳負荷
精神病性症狀
妄想
幻覺
family-based association
schizophrenia
genetic loading
psychotic symptoms
delusion
hallucination
Type
thesis