Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population.
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.
Kwak
S H
SH
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Cho
Y M
YM
Moon
M K
MK
Kim
J H
JH
Park
B L
BL
Cheong
H S
HS
Shin
H D
HD
Jang
H C
HC
Kim
S Y
SY
Lee
H K
HK
Park
K S
KS
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
D007339:Insulysin