Polymorphisms in type IISH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome
Polymorphisms in type IISH2 domain-containing inositol 5-phosphatase (INPPL1, SHIP2) are associated with physiological abnormalities of the metabolic syndrome
复制标题
DOI：
10.2337/diabetes.53.7.1900
复制
发表时间：
2004-07-01
期刊：
影响因子：
7.7
通讯作者：
Gauguier, D
中科院分区：
文献类型：
--
作者：
Kaisaki, PJ;Delépine, M;Gauguier, D
II型含SH 2结构域的肌醇5-磷酸酶（INPPL 1或SHIP 2）在控制胰岛素敏感性中起重要作用。在2型糖尿病和高血压大鼠模型以及2型糖尿病患者中发现了影响基因功能的INPPL 1突变。我们研究了INPPL 1中核苷酸变异对代谢综合征组分的影响。在对该基因进行全面的重新测序后，我们对来自424个英国2型糖尿病家族的1,304名个体进行了12种信息多态性的基因分型，这些个体具有几种代谢表型的特征。我们已经发现INPPL 1的单核苷酸多态性（SNPs）和单倍型与高血压以及代谢综合征的其他组分高度显着相关。在905名法国2型糖尿病患者的队列中，我们发现INPPL 1 SNP与高血压存在相关性的证据。我们的结论是，INPPL 1变异可能会影响疾病的易感性和/或参与代谢综合征在一些糖尿病患者的亚表型。
Type II SH2 domain-containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity. INPPL1 mutations affecting gene function have been found in rat models of type 2 diabetes and hypertension and in type 2 diabetic patients. We investigated the influence of nucleotide variation in INPPL1 on components of the metabolic syndrome. Following comprehensive resequencing of the gene, we genotyped 12 informative polymorphisms in 1,304 individuals from 424 British type 2 diabetes families that were characterized for several metabolic phenotypes. We have found highly significant associations of single nucleotide polymorphisms (SNPs) and haplotypes of INPPL1 with hypertension as well as with other components of the metabolic syndrome. In a cohort of 905 French type 2 diabetic patients, we found evidence of association of INPPL1 SNPs with the presence of hypertension. We conclude that INPPL1 variants may impact susceptibility to disease and/or to subphenotypes involved in the metabolic syndrome in some diabetic patients.