組織胺甲基轉換酶基因與精神分裂症之早發型及持續性注意力缺損之家族關聯研究

目的：利用家關聯性分析探討組織胺甲基轉換酶基因（HNMT）和精神分裂症之早發型及持續性注意力缺損之家族之間的關係。方法：此研究樣本使用排序子集之連鎖分析（OSA）從台灣連鎖精神分裂症研究（TSLS）選取出206個早發且持續性注意力缺損家庭。所有參與研究的個案均由受過訓練的研究助理進行遺傳診斷問卷（DIGS）的訪談與抽血。使用ABI7900進行HNMT上的6個單核苷酸多型性（SNP）的鑑定，並採用FBAT軟體來家族資料之單一基因座與半形關聯性分析。並且使用SNPSpD軟體執行有效標記數量之估計，以便進行多重檢定之校正。結果：針對206個家庭進行單一基因座關聯性分析當中，沒有任何人的單核苷酸多型性與精神分裂症有相關性存在。另外進行兩、三、四、五、六個標記之半形關聯性分析後，我們發現在Nyholt所提出之多重檢定校正方法下，rs3100701－rs3791244－rs3791242－rs11558538半形與有早發性及持續性注意力缺損之精神分裂症家庭有相關存在。結論：根據研究中之初步統計結果，我們推論在HNMT基因與早發性及持續性注意力缺損之精神分裂症家庭之間是有相關性存在，因此在未來當中使用獨立樣本再次進行分析是必須的。

關鍵字

家族關聯性；組織胺甲基轉換酶基因；精神分裂症；早發型；持續性注意力缺損

並列摘要

Objective. To examine the association between histamine N-methyltransferase (HNMT) gene and schizophrenia with early onset and sustained attention deficit using family-based association. Methods. The families in this study were part of the sample from the Taiwan Schizophrenia Linkage Study (TSLS) on the basis of a previous ordered subset analysis (OSA): 206 families of patients with early onset and sustained attention deficits. All participants were interviewed by trained research assistants who used the Diagnostic Interview for Genetic Studies (DIGS), and drawn for peripheral blood. Six SNPs of the HNMT gene were genotyped and FBAT program was used to perform single-locus and haplotype association analyses. Multiple testing was adjusted by means of effective marker number estimated using SNPSpD program. Results. There was no association between individual SNPs of HNMT and schizophrenia in this subset of families. When employing two-, three-, four-, five-, and six-marker sliding window analysis for haplotype association in these families, the result for the four-marker haplotype of rs3100701-rs3791244-rs3791242-rs11558538 haplotype A-G-T-G with schizophrenia had a p-value of 0.012, which was smaller than the threshold for significance (0.013) when adjusted for the effective marker number of four in this study. Conclusions. There was a significant association between HNMT gene and schizophrenia with early onset and sustained attention deficits, and future replication in independent samples is warranted

並列關鍵字

family-based association ； histamine N-methyltransferase ； schizophrenia

參考文獻

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組織胺甲基轉換酶基因與精神分裂症之早發型及持續性注意力缺損之家族關聯研究

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