來自臺灣中央研究院國家基因型鑒定中心主任，臺灣中國醫(yī)藥大學(xué),，臺灣大學(xué)醫(yī)學(xué)院等處的研究人員發(fā)現(xiàn)了漢族人特有的II型糖尿病致病基因，這項創(chuàng)新的研究成果不僅可增進對于第二型糖尿病致病機制之了解,，未來亦有助于糖尿病新藥的設(shè)計與開發(fā),。這一研究成果公布在2月19日國際重要專業(yè)期刊PLoS Genetics上。
糖尿病是危害人類健康的隱形殺手,，是十大死因之一,，臺灣約有120萬糖尿病人口，60萬人已罹患糖尿病而不自知,；醫(yī)療費用占健保經(jīng)費的8分之1,；根據(jù)國際糖尿病聯(lián)盟估計，全球約有3億6千萬人罹患II型糖尿病,，占全球60億人口的6%,，約每5秒就有一人罹患糖尿病,，每10秒就有一人因糖尿病死亡，因而成為世界各國重視的公共衛(wèi)生議題,。
在這篇文章中,，研究人員利用高密度基因型鑒定方法分析了2798位II型糖尿病患的基因，找出了II型糖尿病致病基因PTPRD(位于第9號染色體)與SRR(位于第17號染色體),，這是全球首次發(fā)現(xiàn)且為漢族人特有的致病基因,。PTPRD基因可能影響身體產(chǎn)生胰島素阻抗性，也就是身體細(xì)胞對胰島素的反應(yīng)不良,，因而無法正常吸收代謝血糖,。SRR基因變異推測可能影響胰臟信號傳導(dǎo)(glutamate signaling)，進而改變胰臟的胰島素的分泌,。
這項研究歷時3年,，研究排除原住民、新移民后,，先后掃描了995和894例II型糖尿病患的基因,，找到這兩種特異基因，確認(rèn)相同疾病會因各種族的不同,，致病基因也會有所不同,，之前這一研究小組還在日本和歐洲裔身上發(fā)現(xiàn)了II型糖尿病致病基因KCNQ1，這在漢族人的II型糖尿病的致病機制上也扮演重要角色,。
這一研究是一項重要的進展,，尤其是目前II糖尿病的并發(fā)癥很多，例如白內(nèi)障,、腎衰竭,、青光眼、冠心病,、視網(wǎng)膜病變,、神經(jīng)病變、腦中風(fēng),、組織壞死甚至要截肢等,。
II型糖尿病是新陳代謝異常的慢性疾病，起因是體內(nèi)胰島素對血糖控制的反應(yīng)不夠敏感所致,，與先天性自體免疫導(dǎo)致胰島素缺乏的第一型糖尿病不同,，又易與遺傳基因、飲食,、運動等環(huán)境因子有關(guān),。
研究人員融合臨床經(jīng)驗，并結(jié)合基因組數(shù)據(jù),，先是找到了上千名患者進行全基因組掃描,，再與正常人基因組比對分析,，之后擴大到另外千名患者的相關(guān)基因數(shù)據(jù)，從而確認(rèn)了這兩種基因,，研究人員表示人體內(nèi)有30億對DAN,，他們僅鎖定了55萬個容易變異的DNA進行全基因掃描，竟能只花3年就比對找到特異基因,，運氣算是很好了,。
未來研究人員與公共衛(wèi)生、社區(qū)醫(yī)療照護結(jié)合,，找出與這些并發(fā)癥有關(guān)的遺傳因子,，期能提供更全方位的醫(yī)療照顧與預(yù)防治療，而且這項研究也有助未來糖尿病新藥的設(shè)計與開發(fā),。（生物谷Bioon.com）
II型糖尿病致病基因：
PLoS Genet：發(fā)現(xiàn)II型糖尿病新致病基因及其抑制因子
Diabetologia：發(fā)現(xiàn)一個新的Ⅱ型糖尿病易感基因
Nature Genetics：發(fā)現(xiàn)與Ⅱ型糖尿病相關(guān)基因
Diabetes：發(fā)現(xiàn)2種糖尿病易感基因
Nature Genetics：新發(fā)現(xiàn)6種Ⅱ型糖尿病基因
生物谷推薦原始出處：
PLoS Genet 6(2): e1000847. doi:10.1371/journal.pgen.1000847
A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese
Fuu-Jen Tsai1,2,3#, Chi-Fan Yang4,5#, Ching-Chu Chen6,7#, Lee-Ming Chuang8, Chieh-Hsiang Lu9, Chwen-Tzuei Chang6,7, Tzu-Yuan Wang6,7, Rong-Hsing Chen6,7, Chiung-Fang Shiu4, Yi-Min Liu4, Chih-Chun Chang4, Pei Chen4, Chien-Hsiun Chen4,5, Cathy S. J. Fann4, Yuan-Tsong Chen4,5,10*, Jer-Yuarn Wu4,5,11*
1 School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan, 2 Department of Medical Genetics, Pediatrics and Medical Research, China Medical University Hospital, Taichung, Taiwan, 3 Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan, 4 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, 5 National Genotyping Center, Academia Sinica, Taipei, Taiwan, 6 Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, 7 School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan, 8 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, 9 Department of Internal Medicine, Endocrinology and Metabolism, Chia-Yi Christian Hospital, Chia-Yi, Taiwan, 10 Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States of America, 11 Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement ofKCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.
