Sano R, Miki T, Suzuki Y, Shimada F, Taira M, Kanatsuka A, Makino H, Hashimoto N, Saito Y
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8670, Chiba, Japan.
Diabetes Res Clin Pract. 2001 Nov;54(2):79-88. doi: 10.1016/s0168-8227(01)00287-x.
We screened for mutations in the gene of insulin-sensitive phosphodiesterase 3B (PDE3B), which regulates antilipolytic actions of insulin via reduction of intracellular cyclic AMP levels, in Japanese patients with type 2 diabetes mellitus and lipoatrophic diabetes mellitus using single-stranded conformation polymorphism analysis and Southern analysis and investigated frequencies of variable number of tandem repeats. A silent polymorphism at the Arg463 codon (AGG-->AGA) in exon 4 was identified after examining all 16 exons and exon-intron splicing junctions of the gene. This polymorphism was found in 53 of 100 subjects with type 2 diabetes mellitus, 2 of 5 lipoatrophic diabetic patients and 24 of 50 control subjects, without any significant difference in allele frequency between groups. An EcoRI restriction fragment length polymorphism was identified in patients with type 2 diabetes mellitus and control subjects, again with no differences in occurrence. The allelic distribution of two polymorphic tandem repeats sequences in introns 5 and 12 of the gene did not differ significantly between patients with type 2 diabetes mellitus and control subjects. In conclusion, alterations in the PDE3B gene are unlikely to contribute importantly to the pathogenesis of type 2 diabetes mellitus or lipoatrophic diabetes mellitus in Japan.
我们采用单链构象多态性分析和Southern分析，对日本2型糖尿病和脂肪萎缩性糖尿病患者胰岛素敏感性磷酸二酯酶3B（PDE3B）基因的突变进行了筛查，该酶通过降低细胞内环磷酸腺苷水平来调节胰岛素的抗脂解作用，并研究了串联重复序列可变数目的频率。在检查该基因的所有16个外显子和外显子-内含子剪接连接点后，在第4外显子的Arg463密码子（AGG→AGA）处发现了一个沉默多态性。在100例2型糖尿病患者中有53例、5例脂肪萎缩性糖尿病患者中有2例以及50例对照受试者中有24例发现了这种多态性，各组之间的等位基因频率无显著差异。在2型糖尿病患者和对照受试者中发现了一种EcoRI限制性片段长度多态性，其发生率同样无差异。该基因第5和第12内含子中两个多态性串联重复序列的等位基因分布在2型糖尿病患者和对照受试者之间无显著差异。总之，在日本，PDE3B基因的改变不太可能对2型糖尿病或脂肪萎缩性糖尿病的发病机制起重要作用。
