台湾原住民痛风之流行病学研究

【外文题名】The Epidemiological Study of Gout in Taiwan Aborigines

【作者】 章顺仁

【关键词】 痛风 尿酸 原住民

【外文关键词】 HPRT Gout HPRT Uric acid Aborigines

【导师姓名】葛应钦

【学位名称】博士

【学位年度】暂无

【学位授予单位】暂无

【所属分类】R18

【录入时间】2014-11-17

【全文挂接】 读秀挂接

【摘要】率及其相關
因子；第二部份探 討台灣原住民成人的痛風盛行率及其有關的因子。 我
們採挨家 挨戶的方式訪問 40 歲以上的成人，該受訪者的痛風疾病是由
受 訪者自己提報，但痛風的認定則必須有醫師的臨床診斷為標準； 第三
部份對某位有痛風家族性的患者，其母親是鄒族，解出導致 痛風產生的
基因突變，這種基因探討主要是鎖定在 hypoxanthine- guanine
phosphoribosyltransferase gene (HPRT)， 經找出有 HPRT 基因點突變
後，再依此 點 突變篩檢其三代親人及三族原住民兒 童；這三族分別是
鄒族、泰雅族及布農族。所得的結果如下: ( 一 ) 從民國 82 年 7
月至 84 年 3 月共收集到 1214 位 5- 14 歲的兒童作為研究族群；整體
而言高尿酸血症 (血清中 尿酸濃度≧7.5 mg/dl) 有 27.3%
(332/1214)，男女性盛行率分別 為30.4% ，24.2% (186/611，146/603;
p<0.05)；對 各族別而言， 不論是男性或女性泰雅族都有最高的盛行率(
男性 43.1%, 94/218; 女性 39.6%, 82/207), 其次則是排灣族, 非原住
民則為最低(男性 為客家最低, 13.4% ; 女性為閩南最低 5.4%)。經初步
分析及以邏 輯迴歸做校正後發現，有關導致高尿酸血症的因子中，有年
齡、 性別、身體質量指數、族別、三甘油脂和膽固醇濃度等。本篇結論
說明在沒有成人常有的生活嗜好的干擾下(如:抽菸、喝酒和嚼 檳榔)，族
別 (原住民； 包括南部及北部原住民 ) 對血中尿酸濃 度有重要的影響
。 ( 二 ) 共收集 1343位 40歲以上的參與者，結果顯示原住 民男性
及女性的痛風盛行率分別為9.3% (26/281)，及3.0% (11/371)，比起非原
住民( 男女合計 ) 的0.4% 來講，則顯得相 當的高。經邏輯回歸調整干
擾因子後，發現男性原住民且有高尿 酸血症者(血清中尿酸濃度在男性>
7.0 mg/dl, 在女性為 >6.0 mg/dl)比較容易患有痛風 (p<0.05 ) 。在探
討高尿酸血症的相關因 子上，結果顯示高尿酸血症比較容易發生在 、三
甘油脂在 170 mg/dl 以上、腰臀比在 0.9 以上的原住民。本研究顯示台
灣原住 民有如此高的痛風盛行率，而種族因子為其主要的相關因子。
( 三 ) 本研究從母親為鄒族的一位痛風患者身上，從 HPRT cDNA 序列上
找出一個新的點突變，此點突變位於 HPRT cDNA 的第 152 核甘酸，此核
甘酸基原本是G ，經突變後成為 A 。 這個突變將第51胺基酸原本是精氨
酸 (arginine) 轉成麩醯胺 (glutamine ) 。我們依照此位痛風患者的母
親族別將此突變命名 為 HPRTTsou 。此 突變確定後，再以聚合脢鍊結反
應及 Restriction Fragment Length Polymorphism 法篩檢此位痛風患者
的家人、鄒 族的小孩，以及泰雅族及布農族的小孩。結果顯示，此位痛
風患 者的七位兄弟姊妹中(含自己)有六位遺傳到此突變，八位兄弟姊 妹
的小孩則有4 位從他的母親遺傳到此突變。此時，我們也篩檢 70 位泰雅
族小 孩、 76 位布農族小孩及 22位鄒族小孩， 結果 發現有兩位小孩
( 一位泰雅族及一位鄒族 ) 遺傳到此突變。 從以上結果可知，無論
是高尿酸血症或是痛風盛行率，對原 住民來講都比非原住民有較高的盛
行率，而種族則是一項重要的 相關因子。在進一步分析影響痛風的基因
時，發現在有鄒族血統 的痛風患者身上的 HPRT 有一新的突變，然而這
種突變在泰雅族小孩及鄒族小孩上的分佈並不高( 1.4%;1/70， 4.5% ;
1/22)。 是否另有其他的基因變異會導致原住民產生痛風則有待更進一步
的探討。 本研究首先突顯原住民小孩有較高的高尿酸血症盛行率，而
且其同族的成人裡不但高尿酸血症盛行率高連痛風盛行率也高， 再經排
除環境因子的干擾後，很顯然的這種高痛風盛行率是與原 住民有很強的
相關；況且我們也在有鄒族血源的痛風患者身上找 到會導致尿酸累積的
基因突變(HPRTTsou )，然而此基因突變在各 族小孩的盛行率並不高，
我們相信在原住民中應還有其他的基因 變異會導致尿酸的累積，而這種
基因可能存在體染色體。...

【外文摘要】The epidemiological study of gout in Taiwan Aborigines(1998) The Graduate Institute of MedicineThe Graduate student : Shun-Jen Chang, Adviser: Ying-Chin KoStudent No: 8381005Abstract There are three aboriginal tribes (Bunun, Paiwan and Atayal) and twonon-aborigines (Fukien-Taiwanese and Hakka ) were included as study''spopulation. This study was divided into three parts, the first subject wasto explore the hyperuricemic prevalence and related factors from the abovefive populations whose age were between five and 14 years. The secondsubject focused the adult''s gout and hyperuricemic prevalence and therelated factors. We visited the persons whose age great than 40 years bydoor to door, the gout disease was self-reported from the subject and hadbeen identified by a practical doctor. The third was to reveal the HPRT genefrom a severe gout patient who was with gout pedigree, after finding themutation from the patient, then by using PCR-RFLP method to screen hisfamilies and three tribes'' children. The results showed that (1) there were 1214 children had been includedin this study from the five tribes between Jul 1993 and Mar 1994; Overall,the hyperuricemic ( uric acid ≧ 7.5 mg/dl) prevalence was 27.3% (332/1214),the hyperuricemic rate among male was 30.4%, and 24.2% among female andthere was statistical difference among sex (186/611, 146/ 603; p<0.05). TheAtayal tribe, no matter male or female, had the highest prevalence ofhyperuricemia, the Paiwan tribe followed, and the non-Aboriginal tribes thelowest. After the preliminary and logistic regression model adjusted theconfounders, the result showed that the factors related to hyperuricemia hadage, sex, body mass index, tribes, the serum triglycerides and cholesterolconcentration. Without the interference of the living habits in adults such as tobaccosmoking, alcohol consumption and betel nut chewing, the factor of Aborigineshad major effect on serum uric acid was concluded. (2) The prevalence of gout disease among aboriginal male and female were9.3% (26/281) and 3.0% (11/371), which were significant higher than thenon-aborigines (0.4% in both male and female). The related factors of goutdisease were explored by logistic regression model, and found that theaboriginal men with hyperuricemia tended to get the gout disease. About thefactors related to hyperuricemia showed that the aborigines withtriglycerides over 170 mg/dl and the ratio of waist line over hip linegreater than 0.9 were likely to have hyperuricemia. The factor of tribe havethe major effect on the onset of gout disease was included. (3) One new mutation locate at the HPRT cDNA 152 nucleotide was foundfrom a severe gout patient (proband) whose mother originated from Tsou tribe, thus the mutation was named as HPRTTsou according to his mother''s tribe. The mutation cause the nucleotide transition from G to A which cause the 51amino acid transgression from argentine to glutamate. After that, wescreened the proband''s families, the children from Tsou''s tribes, Atayaltribe and Bunun tribe by using the PCR-RFLP method. The results showed that85.7% (6/7) of the proband''s siblings had HPRTTsou from their mother, andalso there were 50% (4/8) of the children of proband''s siblings inheritedthis mutation from their carried mother. Among the children, only twofemales had this mutation which one from Atayal tribe and one from Tsoutribe. In conclusion, no matter the hyperuricemia or gout disease, theAborigines have the higher prevalence than non-aborigines, thus the tribefactor may be considered as a most important factor. In another hand, theHPRTTsou distribute low prevalence among Atayal tribe and Tsou tribe (1.4%;1/70, 4.5%; 1/22, respectively). This study showed that both of the aboriginal children and adults havehigh prevalence of hyperuricemia, and the gout disease also predominated inthe Aborigines. Furthermore, there was a HPRT point mutation would cause theuric acid accumulated existed in the Tsou tribe''s offspring. Th...