Polymorphisms in the insulin-degrading enzyme gene are associated with type 2 diabetes in men from the NHLBI Framingham Heart Study.
Linkage studies have mapped a susceptibility gene for type 2 diabetes to the long arm of chromosome 10, where we have previously identified a quantitative trait locus that affects fasting blood glucose within the Framingham Heart Study cohort. One candidate gene in this region is the insulin-degrading enzyme (IDE), which, in the GK rat model, has been associated with nonobese type 2 diabetes. Single nucleotide polymorphisms (SNPs) were used to map a haplotype block in the 3' end of IDE, which revealed association with HbA(1c), fasting plasma glucose (FPG), and mean fasting plasma glucose (mFPG) measured over 20 years. The strongest associations were found in a sample of unrelated men. The lowest trait values were associated with a haplotype (TT, f approximately 0.32) containing the minor allele of rs2209772 and the major allele of the rs1887922 SNP (FPG P < 0.001, mFPG P < 0.003, HbA(1c) P < 0.025). Another haplotype (CC, f approximately 0.16) was associated with elevated HbA(1c) (P < 0.002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28-3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent.
Karamohamed
Samer
S
Framingham Heart Study Genetics Laboratory, Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Demissie
Serkalem
S
Volcjak
Jeannine
J
Liu
Chunyu
C
Heard-Costa
Nancy
N
Liu
Jun
J
Shoemaker
Christina M
CM
Panhuysen
Carolien I
CI
Meigs
James B
JB
Wilson
Peter
P
Atwood
Larry D
LD
Cupples
L Adrienne
LA
Herbert
Alan
A
D001786:Blood Glucose / Q000378:metabolism; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012727:Sex Characteristics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D001786:Blood Glucose; D007339:Insulysin