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Please use this identifier to cite or link to this item: http://ir.hwai.edu.tw:8080/ir/handle/310996100Q/1638

Title: MAPK8IP1基因單一核苷酸多型性對情感性疾患的影響研究
Effects of Single Nucleotide Polymorphism of MAPK8IP1 Gene on Mood Disorders
Authors: 柳雅馨
Liu, Ya Hsin
Keywords: 憂鬱症
躁鬱症
家族聚集
MAPK8IP1基因
啟動子
Major depression disorder
bipolar disorder
familial aggregation
MAPK8IP1 gene
promoter
Date: 2013
Issue Date: 2013-11-01 10:54:02 (UTC+8)
Abstract: 研究背景:情感性疾患主要是重度憂鬱症(MDD)和躁鬱症(BPD,包括BPI和BP II),在一般人群中是常見的。然而,很少有人知道他們的臨床特點和MAPK8IP1基因的單一核苷酸多型性關係。
目的:研究MAPK8IP1基因單一核苷酸多型性與臨床特徵的關係及對MAPK8IP1基因啟動子活性的影響。
材料與方法:透過家族研究設計,共收集了1242人參加,其中包括464位個案,522個家屬和256位健康對照組,從2008至2012年在台灣南部和北部的六個地區醫院或診所收集。經由受訓過的訪員作為訪談,採用複合性國際診斷問卷訪談(CIDI)收集資料,人口統計學和臨床特徵。然後建構了啟動子上MAPK8IP1gene,伴有精神疾病或應對環境因素,並比較了不同的基因型在神經細胞上的活性變化。我們還研究了這些變化的相關性,與高壓下的精神疾病患者的表現。
結果:使用匹茲堡睡眠品質量表來評估在過去一個月的睡眠情況,在個案、家屬及健康對照組間進行比較,除睡眠時間不顯著外(P= 0.274),其他項目都有統計上的顯著性,包括睡眠品質(P <0.001)、睡眠潛伏期(P<0.001)、睡眠效率(P <0.001)、睡眠困擾(P <0.001)、使用藥物(P <0.001)和白天功能障礙(P <0.001)等。探討基因變異與情緒障礙行為之間的關係時發現,各種情緒障礙與MAPK8IP1基因單一核苷酸多型性(SNP) rs1554338位點沒有顯著相關。但自殺行為在病患組AA/AG與GG比較,接近顯著性(P= 0.059)。探討rs1554338位點與身體質量指數(BMI)及糖尿病的關係,發現並無顯著的影響。在啟動子分析實驗上,比較rs1554338位點A與G對MAPK8IP1基因啟動子的影響,發現沒有顯著差異,為進一步探討這位點對基因表現的重要性,將之突變為T則明顯降低啟動子活性。
結論:情緒障礙與睡眠品質量表,包括睡眠品質,睡眠潛伏期,睡眠效率,睡眠困擾,藥物和白天功能障礙均有顯著性。除自殺外,情緒障礙及BMI與糖尿病和SNP MAPK8IP1基因分型無相關。但MAPK8IP1基因rs1554338位點與啟動子活性有關。
Backgrounds: Affective disorders, mainly depressive (MDD) and bipolar disorders (BPD, including BP I and BP II), are common in the general population. However, little is known about the correlation of genetic variation and clinical features.
Objectives: The objectives of this study are to correlate SNP of MAPK8IP1 gene with clinical features and to study the effects of this SNP on promoter activity.
Materials and Methods: There were 1242 participants, including 464 probands, 522 relatives and 256 controls ascertained from six regional hospitals or clinics in the Southern and Northern Taiwan from 2008 to 2012. Participants were interviewed by well-trained interviewers using Composite International Diagnostic Interview (CIDI) to collect data on demographic and clinical features. The data were collected from the interviews of patients with depression or bipolar disorder, their families and healthy people. Then we cloned the promoter of MAPK8IP1 gene, which is associated with mental diseases or responding to environmental factors, and compared the promoter activities between the promoters containing different variations. We also studied the correlation of these alleles with performance of patients suffered by mental diseases.
Results: Pittsburgh Sleep Quality Index, PSQI, was used to assess the past month sleep situation. There were significant differences among probands, relatives and controls in six items, including sleep quality (p<0.001), sleep latency (p<0.001), sleep efficiency (p<0.001), sleep disturbances (p<0.001), use of medications (p<0.001) and day-life dysfunction (p<0.001). However, sleep duration was not significant (p=0.274). We then analyze the correlation of mood disorders and SNP (rs1554338) of MAPK8IP1 gene and found that there was no significance.
However, it is more significant in suicide between MAPK8IP1 genotypes, AA/AG vs GG in patients (P=0.059). In addition, rs1554338 does not correlate to BMI or diabetics. We also found that promoter activities of MAPK8IP1 gene on A and G alleles are similar. However this site is important for MAPK8IP1 gene expression, because mutation of allele A or G to T decreased promoter activity significantly.
Conclusion: Mood disorder is associated with sleep quality, including quality, latency, efficiency, disturbances, medications and dysfunction. Except for suicide, mood disorders are not associated with SNP on MAPK8IP1 promoter. The site of MAPK8IP1 rs1554338 is important for promoter activity.
Appears in Collections:[生物科技系暨生物醫學研究所] 博碩士論文

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