title: Polymorphisms in the insulin-degrading enzyme gene are associated with type 2 diabetes in men from the NHLBI Framingham Heart Study.
abstract: 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.
authors.affiliation: Framingham Heart Study Genetics Laboratory, Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Karamohamed
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: Jeannine
authors.initials: J
authors.lastname: Volcjak
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.forename: Nancy
authors.initials: N
authors.lastname: Heard-Costa
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Christina M
authors.initials: CM
authors.lastname: Shoemaker
authors.forename: Carolien I
authors.initials: CI
authors.lastname: Panhuysen
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.forename: Peter
authors.initials: P
authors.lastname: Wilson
authors.forename: Larry D
authors.initials: LD
authors.lastname: Atwood
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Alan
authors.initials: A
authors.lastname: Herbert
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007339:Insulysin