title: Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population.
abstract: Insulin-degrading enzyme (IDE) is a metalloproteinase which degrades insulin and terminates its action. Homologous deletion of IDE gene resulted in hyperinsulinemia and glucose intolerance in a rat model of type 2 diabetes mellitus. Several genetic association studies examined IDE as a susceptibility gene for type 2 diabetes in European descents. Here we investigated the genetic association of IDE polymorphisms with the risk of type 2 diabetes and its related phenotypes in the Korean population. Among six single nucleotide polymorphisms analyzed, g.-179T>C (OR=1.73, P=0.04), and g.IVS18+99G>A (OR=1.23, P=0.02) revealed borderline association with increased risk of type 2 diabetes. Combining our results with previous data obtained from the European population, g.-179T>C (OR=1.11, P=0.03), and g.IVS24-64A>T (OR=1.18, P=0.005) showed significant association with type 2 diabetes. Haplotype consisting of common alleles of the six polymorphisms was associated with decreased risk of type 2 diabetes (OR=0.82, P=0.02). However, none of the polymorphisms was significantly associated with metabolic phenotypes. We can conclude that variations in IDE might contribute to diabetes susceptibility in the Korean population.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kwak
authors.forename: Y M
authors.initials: YM
authors.lastname: Cho
authors.forename: M K
authors.initials: MK
authors.lastname: Moon
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: B L
authors.initials: BL
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Cheong
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
authors.forename: H C
authors.initials: HC
authors.lastname: Jang
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: H K
authors.initials: HK
authors.lastname: Lee
authors.forename: K S
authors.initials: KS
authors.lastname: Park
mesh_terms: D000368:Aged; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D018570:Risk Assessment
chemical_list: D007339:Insulysin