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研究生:江建華
研究生(外文):Chiang, Chien-Hua
論文名稱:利用PCR-SSP技術對中國人孩童期發作胰島素依賴型糖尿病人其HLA-DQA1,-DQB1對偶基因之研究
論文名稱(外文):The Studies of HLA-DQA1, -DQB1 Alleles for Child Onset Insulin- Dependent Diabetes Mellitus Patients in Chinese by Using PCR-SSP
指導教授:陳 百 薰
指導教授(外文):Chen Bai-Hsiun
學位類別:碩士
校院名稱:高雄醫學院
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:1998
畢業學年度:86
語文別:中文
論文頁數:2
中文關鍵詞:胰島素依賴型糖尿病遺傳易感性發作年齡性別
外文關鍵詞:DQA1-DQB1 基因型PCR-SSPIDDMgenetic susceptibilityage at onsetgenderDQA1-DQB1 genotypePCR-SSP
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胰島素依賴型糖尿病(Insulin-dependent diabetes mellitus, IDDM) 乃
是病原不明的自體免疫性疾病.然而環境及遺傳此兩因素在引起疾病方面
所拌演的角色皆顯得相當重要.容易罹患此疾病之個體,在人類第六對染色
體之主要組織相容性複體(major histocompatibility complex, MHC)上
有特異性的基因型存在.而在人類主要組織相容性複體中,人類白血球組織
抗原DQ (HLA-DQ) 則顯示出和胰島素依賴型糖尿病有著最強烈的關聯性.
除了種族和地理區域外,發病年齡及性別也可以影響此關聯性.為了更進一
步闡明HLA-DQA1及HLA-DQB1和胰島素依賴型糖尿病之關聯性,並且了解發
病年齡及性別的影響,我們利用更迅速且具較高解析力之聚合酵素鏈鎖合
成反應合併序列特異性引子 (polymerase chain reaction with
sequence-specific primers, PCR-SSP) 分析的方法,對所收集的檢體進
行HLA-DQA1及HLA-DQB1基因型分類.本研究共收集54位沒有親戚關係且其
發病年齡均在孩童時期的胰島素依賴型糖尿病患者 (平均發病年齡8.37
+/- 3.54歲) 及65位健康個體,分別作為本實驗之研究組及對照組.本研究
之對象均為居住在南台灣的中國人.結果顯示,對偶基因HLA-DQA1*0301,
DQA1*0302, DQB1*0201, DQB1*0302在研究組中的比率,比對照組高
(P<0.025, P<0.005, P<0.001, P<0.001, respectively).保護性的對偶
基因分別為DQA1*0101, DQA1*0103, DQB1*0301, DQB1*0501, DQB1*0503
及DQB1*0602 (P<0.001, P<0.005, P<0.001, P<0.025, P<0.025,
P<0.025, respectively). 我們亦發現在不同發病年齡群 (1-5歲,6-10
歲, 11-15歲) , DQA1*0302在研究組中的比率會隨著發病年齡群年紀的增
加而增加.在本實驗研究組的病患中,男性有21位,女性有33位.男性病患較
女性病患有較多之DQA1*0501, DQB1*0201基因型 (P均小於0.025) , 而女
性則有較高比例的DQA1*0102 (P<0.05) . 總之, 針對國人孩童時期發作
胰島素依賴型糖尿病的研究結果中, 不僅顯示疾病的易感性及保護性和特
定的對偶基因及能賦予密碼來合成DQ alfa-beta 分子的DQA1-DQB1 基因
型有關,並且証明發病年齡和性別,也是影響HLA-DQ和胰島素依賴型糖尿病
之間關聯性的因素之一.
Type I (insulin-dependent) diabetes mellitus is an autoimmune
disease of uncertain aetiology. Both the roles of environmental
and genetic factors appear important. From the genetic point of
view, inherited susceptibility has been mapped to the major
histocompatibility complex (MHC) on chromosome 6. Among the MHC,
the association of IDDM and MHC is strongest with the HLA-DQ
subregion. The relationship between HLA and IDDM could be
influenceed by gender and age at onset, not by ethnic groups and
geographical region. To further elucidate the association of
HLA-DQA1 and DQB1 with IDDM as well as the influence of age at
on set and gender, we investigated 54 unrelated childhood onset
IDDM patients and 65 healthy control subjects among Chinese
living in Taiwan using PCR amplification with sequence-specific
primers (PCR-SSP) methods. This method is an accurate and rapid
technique for detecting genetic variablity with a high degree of
resolution. Our study revealed that the frequencies of
DQA1*0301, DQA1*0302, DQB1*0201 and DQB1*0302 alleles were
significantly increased in IDDM patients than those in the
controls (P<0.025, P<0.005, P<0.001, P<0.001, respectively). The
protective alleles were DQA1*0101, DQA1*0103, DQB1*0301,
DQB1*0501, DQB1*0503 and DQB1*0602 (P<0.001, P<0.005, P<0.001,
P<0.025, P<0.025, P<0.025, respectively). We also found that the
frequency of DQA1*0302 decreased with increase of age groups
(age onset 1-5, 6-10 and 11-15 years). the frequencies of
DQA1*0301, DQA1*0501 increase of age groups. In this study, 54
juvenile IDDM patients consist of 21 males and 33 females.
DQA1*0501 and DQB1*0201 were present more frequently in male
patients than in female ones (both P<0.025). However, female
patients had a higher percentage of DQA1*0102 than that of male
patients (P<0.05). Our result indicated that susceptibility and
resistance to IDDM were associated with particular alleles and
DQA1-DQB1 genotypes encoding DQ alfa-beta heterodimers.
Additionally, age at onset and gender were important factors
that could influence the associations of HLA-DQ with IDDM.
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