原住民族群(Atayal ,泰雅)URAT1蛋白對應GENE SLC22A12上rs893006 SNP位點於高尿酸血症患者中之表現

Association between rs893006 SNP of gene SLC22A12 encoding URAT1 (urate transporter protein) and the hyperuricemia in Taiwanese aborigines (Atayal)

石瑄(Hsuan Shih)

指導教授 ： 謝銘勳

臺北醫學大學/醫學院/臨床醫學研究所/碩士(2009年)

https://doi.org/10.6831/TMU.2009.00074

摘要

尿酸是人體嘌呤代謝後的最終產物(ATP, GTP & nucleic acid), 而人體的尿酸經由製造和排出維持一定的濃度.當尿酸在體內的濃度過高時, 會很容易累積在關節周圍, 刺激發炎,腫脹,發熱, 引起嚴重的疼痛, 甚至久了會形成痛風石, 破壞關節組織, 包括肌腱及骨頭部份.當疼痛發生時, 造成相當大的痛苦, 有人形容成風吹過也疼痛不已, 故也叫做痛風.
一直以來, 尿酸經由何種模式代謝, 其最終對人體是不是無任何幫助, 只會產生疾病, 尚未有定論. 但已知的是尿酸對人體而論, 似乎不是一無是處. 在一些特定情況下, 尿酸可以是一種強的抗氧化物,當缺乏鹽類時, 還可以經由血管收縮素做用, 扮演穩定血壓的重要角色.
近端腎小管頂點蛋白URAT1(coded by SLC22A12), 對尿酸經由腎臟的排出及再吸收所扮演的角色, 重要性似乎是愈來愈明顯, 而陸續有一些新的報告針對SLC22A12其核酸多樣性對尿酸代謝的影響關係被定性出來.經由326位日本人之SLC22A12 gene, 點rs893006單核苷酸多態性(single neucleotide polymorphism, SNP) (GG, GT and TT) 之分析, 發現血液中高尿酸值與SLC22A12 基因中之單核苷酸多態性有明顯相關.
在台灣原住民中, 有明顯的高尿酸血症之發生率. 我們採取368位志願者之血液, 包括175位男性受試者及193位女性受試者. 分別為原住民235位(泰雅族、布農族、排灣族)和平地人133位. 淋巴球純化出DNA, 檢視SLC22A12 gene點rs893006單核苷酸多態性(single neucleotide polymorphism, SNP)的基因表現型為何, 其不同基因型對於URAT1蛋白的功能影響與高尿酸血症有何影響, 其關係為何, 是否有意義?
另外, 我們也將同時比較血液樣本中之肌酸酐, 空腹血糖值, 三酸甘油脂, 胆固醇, 基礎體重值與高尿酸血症患者其SLC22A12 gene點rs893006單核苷酸多態性是否有任何相關性.

關鍵字

痛風 ； 尿酸 ； 單核苷酸多態性 ； 台灣原住民

並列摘要

Serum uric acid is the degradation product of purines (ATP, GTP & nucleic acid). Serum uric acid level is maintained by urate synthesis and excretion. Whenever hyperurecemia happened, the joint inflammatory change, cause a lot of pain. The risk of deposition of uric acid around joints will increase, thus cause joint, tendon destruction and disability. The tophus formation and joint destructive process induce very severe pain and disability, which is known as gouty arthritis.
For a long time, uric acid metabolitic process is not been fully understood. Is it really the only final excretional product or if it still has some possible usefulness? The answer is quite clear, under some certain circumstances, it can be function similar to vitamin C, as a potent antioxidant. Also, urate can maintain blood pressure under low salt conditions via stimulation of the reninangiotensin system through a mechanism that is still poorly understood.
The renal tubule apical protein, URAT1 (coded by SLC22CA12) was recently proposed to be the major absorptive urate transporter protein in the kidney regulating blood urate levels. A study of the Janpanese genetic variations in SLC22A12 gene, rs893006 polymorphism (GG, GT and TT) in a total of 326 Japanese subjects was published. The significant correlation between single nucleotide polymorphism (SNP) in the urate transporter gene SLC22CA12 was found to be associated with the elevated serum uric acid levels.
In Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout. We collected 368 volunteers blood samples, which including 175 cases of male and 193 cases of female. (Ataya, Bunun, Paiwan, and general Taiwanese)(including 133 cases of general population of taiwanese as control group, 235 cases are the Taiwanese aborigines(Atayal),) The genomic DNA from peripheral blood lymphocytes will be collected, and use for genotyping of the rs893006 polymorphism in SLC22A12 gene, comparing the difference between Taiwanese aborigines and the general population.
Otherwise, we will also compare the difference between the plasma level of creatinine, fasting plasma glucose level, triglyceride, serum cholesterol, BMI and the serum uric acid level.

並列關鍵字

gout ； uric acid ； single nucleotide polymorphism ； taiwanese aborigines

參考文獻

1. Anzai N et al. The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.

J Biol Chem 279: 45942–45950

2. B Stibůrková Familial juvenile hyperuricemic nephropathy: Localization of the gene on chromosome 16p11.2—and evidence for genetic heterogeneity

Am. J. Hum. Genet. 66:1989–1994, 2000

4. Choi HK, Mount DB, Reginato AM Pathogenesis of gout.