Novel mutations of mitochondrial DNA associated with type 2 diabetes in Chinese Han population
Novel mutations of mitochondrial DNA associated with type 2 diabetes in Chinese Han population
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DOI：
10.1620/tjem.215.377
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发表时间：
2008-08-01
影响因子：
2.2
通讯作者：
Li, Xiao-Hui
中科院分区：
文献类型：
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作者：
Liao, Wen-Qiang;Pang, Yan;Li, Xiao-Hui
线粒体单核苷酸多态性（mitochondrialsinglenucleotidepolymorphisms，mtSNPs）与2型糖尿病（type-2 diabetesmellitus，T2 DM）相关，但不同人群和地区的mtSNPs差异较大。为探讨中国汉族2型糖尿病（T2 DM）患者的线粒体单核苷酸多态性（mtSNPs），对中国西部重庆地区72例T2 DM患者（59 4岁）和50例正常对照者（对照组）的线粒体基因组全序列进行了直接测序和mtSNPs分析。我们发现中国汉族人群中存在M8、M9、D、G、R和A单倍型群，T2 DM患者单倍型群M9的频率显著高于对照组（p = 0.0006，OR 0.06 [95%CI 0.008-0.476]）。发现T2 DM患者中NADH脱氢酶亚基1（ND 1）中的MtSNPs T3394 C、ND 2中的G4491 A、T16189 C和T16519 C的频率显著高于对照组（T16189 C，p = 0.0045; T16519 C，p < 0.0001; T3394 C，p = 0.0015; G4491 A，p = 0.0015）。相比之下，对照组ND 2中C5178 A和ND 3中A10398 G的频率高于T2 DM患者（C5178 A，p = 0.014; A10398 G，p = 0.0011）。结果表明，mtSNPs T3394 C、G4491 A、T16189 C和T16519 C具有T2 DM的易感性，C5178 A和A10398 G可能是T2 DM的遗传易感因素。本研究所发现的mtSNPs可用于中国汉族人群T2 DM的早期诊断和预防。
Mitochondrial single nucleotide polymorphisms (mtSNPs) have been reported to associate with type-2 diabetes mellitus (T2DM), but mtSNPs appear to be considerably different among different populations and regions. To determine mtSNPs in Chinese Han patients with T2DM, the entire sequences of the mitochondrial genomes from 72 T2DM Chinese (59 4 years) and 50 age-matched healthy subjects (controls) in Chongqing region of Western China were directly sequenced and mtSNPs were analyzed. We found that M8, M9, D, G, R and A haplogroups exist in Chinese Han population and the frequency of haplogroup M9 was significantly higher in patients with T2DM than in the controls (p = 0.0006, OR 0.06 [95% CI 0.008-0.476]). MtSNPs T3394C in NADH dehydrogenase subunit 1 (ND1), G4491A in ND2, T16189C and T16519C were found with significantly higher frequency in patients with T2DM than in the controls (T16189C, p = 0.0045; T16519C, p < 0.0001; T3394C,p = 0.0015;G4491A, p = 0.0015). In contrast, the frequency of C5178A in ND2 and A10398G in ND3 was higher in the controls than in patients with T2DM (C5178A, p = 0.014; A10398G, p = 0.0011). Our results indicate that mtSNPs T3394C, G4491A, T16189C and T16519C show susceptible tendency to T2DM and mtSNPs C5178A and A10398G seem to be genetic factors for against T2DM. These mtSNPs determined in our study is useful and could be used for early diagnosis and prevention of T2DM in Chinese Han population.