来自台湾中央研究院国家基因型鉴定中心主任，台湾中国医药大学，台湾大学医学院等处的研究人员发现了汉族人特有的II型糖尿病致病基因，这项创新的研究成果不仅可增进对于第二型糖尿病致病机制之了解，未来亦有助于糖尿病新药的设计与开发。这一研究成果公布在2月19日国际重要专业期刊PLoS Genetics上。
糖尿病是危害人类健康的隐形杀手，是十大死因之一，台湾约有120万糖尿病人口，60万人已罹患糖尿病而不自知；医疗费用占健保经费的8分之1；根据国际糖尿病联盟估计，全球约有3亿6千万人罹患II型糖尿病，占全球60亿人口的6%，约每5秒就有一人罹患糖尿病，每10秒就有一人因糖尿病死亡，因而成为世界各国重视的公共卫生议题。
在这篇文章中，研究人员利用高密度基因型鉴定方法分析了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号染色体)与SRR(位于第17号染色体)，这是全球首次发现且为汉族人特有的致病基因。PTPRD基因可能影响身体产生胰岛素阻抗性，也就是身体细胞对胰岛素的反应不良，因而无法正常吸收代谢血糖。SRR基因变异推测可能影响胰脏信号传导(glutamate signaling)，进而改变胰脏的胰岛素的分泌。
这项研究历时3年，研究排除原住民、新移民后，先后扫描了995和894例II型糖尿病患的基因，找到这两种特异基因，确认相同疾病会因各种族的不同，致病基因也会有所不同，之前这一研究小组还在日本和欧洲裔身上发现了II型糖尿病致病基因KCNQ1，这在汉族人的II型糖尿病的致病机制上也扮演重要角色。
这一研究是一项重要的进展，尤其是目前II糖尿病的并发症很多，例如白内障、肾衰竭、青光眼、冠心病、视网膜病变、神经病变、脑中风、组织坏死甚至要截肢等。
II型糖尿病是新陈代谢异常的慢性疾病，起因是体内胰岛素对血糖控制的反应不够敏感所致，与先天性自体免疫导致胰岛素缺乏的第一型糖尿病不同，又易与遗传基因、饮食、运动等环境因子有关。
研究人员融合临床经验，并结合基因组数据，先是找到了上千名患者进行全基因组扫描，再与正常人基因组比对分析，之后扩大到另外千名患者的相关基因数据，从而确认了这两种基因，研究人员表示人体内有30亿对DAN，他们仅锁定了55万个容易变异的DNA进行全基因扫描，竟能只花3年就比对找到特异基因，运气算是很好了。
未来研究人员与公共卫生、社区医疗照护结合，找出与这些并发症有关的遗传因子，期能提供更全方位的医疗照顾与预防治疗，而且这项研究也有助未来糖尿病新药的设计与开发。（生物谷Bioon.com）
II型糖尿病致病基因：
PLoS Genet：发现II型糖尿病新致病基因及其抑制因子
Diabetologia：发现一个新的Ⅱ型糖尿病易感基因
Nature Genetics：发现与Ⅱ型糖尿病相关基因
Diabetes：发现2种糖尿病易感基因
Nature Genetics：新发现6种Ⅱ型糖尿病基因
生物谷推荐原始出处：
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.
