title: Genetic susceptibility to type 2 diabetic nephropathy in human and animal models.
abstract: Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Hongo, Tokyo, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe-Yamada
authors.forename: Masakazu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kaneko
authors.forename: Shinji
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Kenji
authors.initials: K
authors.lastname: Shiina
authors.forename: Toshihide
authors.initials: T
authors.lastname: Shike
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Funabiki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci
chemical_list: D007703:Peptidyl-Dipeptidase A