早发糖尿病合并肝囊肿家系肝细胞核因子1β基因的突变研究  

Analysis of hepatocyte nuclear factor 1β gene mutations in early-onset diabetes with hepatic cysts pedigrees

作　　者：王亚超[1,2] 郭振奎[1] 荣海钦[1] 

机构地区：[1]山东省内分泌与代谢病研究所,山东济南250062 [2]济南大学山东省医学科学院医学与生命科学学院,山东济南250000

出　　处：《临床荟萃》2013年第6期640-642,645,共4页Clinical Focus

摘　　要：目的探讨早发糖尿病合并肝囊肿家系临床表型与肝细胞核因子(hepatocyte nuclear factor,HNF)1β基因突变的关系,以明确糖尿病合并肝囊肿与青少年起病的成人型糖尿病(MODY)5亚型的关系。方法采集9例早发糖尿病合并肝囊肿家系先证者及16例健康对照者外周血样,提取基因组DNA,应用聚合酶链式反应(Polymerase Chain Reaction,PCR)技术对HNF1β基因序列扩增并测序分析,如先证者发现突变,则进一步对其家属进行研究。结果 9例先证者均未发现HNF1β基因编码区突变,但发现6种非编码区多态性,分别为:IVS7-115G>A,IVS8+102G>A,IVS8+155delA,IVS9-22T>C,+99A>C,+100G>A。其中+99A>C仅见于一个先证者及其子,在对照组没有发现;余5种多肽变异同时出现在患病组和健康对照组。结论该9个早发糖尿病合并肝囊肿家系不是MODY5家系。HNF1β基因下游调控序列+99A>C变异可能与早发糖尿病合并肝囊肿相关。Objective To investigate the correlations between the clinical phenotype of early-onset diabetes with hepatic cysts pedigree and hepatocyte nuclear factor 1β （HNF1β） gene mutation. Methods Genomic DNA was extracted from the peripheral blood samples collected from 9 probands of early-onset diabetes with hepatic cysts pedigrees and 16 healthy subjects. Polymerase chain reaction（PCR） was performed to amplify all the exons and exon/ intron splice sites of HNF1β gene and the products of PCR were sequenced to identify the DNA variants. If the gene mutations were found in the probands,further research was performed in their families. Results No mutation but six polymorphisms were found as follows.. IVS7-115G〉A,IVS8＋102G〉A,IVS8＋155delA,IVS9-22T〉C, ＋99 A〉C, and ＋100G〉A. The ＋99 A〉C polymorphism was only seen in a proband and her son,it was not found in the same location of the other subjects. The other polypeptide variations appeared in both disease and healthy control groups. Conclusion Nine early-onset diabetes with hepatic cysts pedigrees are not MODY5. The ＋ 99 A〉C polymorphism may be associated with early-onset diabetes complicated with hepatic cysts.

关 键 词：糖尿病 2型 囊肿 肝 肝细胞核因子1β 多态性 单核苷酸 

分 类 号：R587.1[医药卫生—内分泌]