High-density haplotype structure and association testing of the insulin-degrading enzyme (IDE) gene with type 2 diabetes in 4,206 people.
The insulin-degrading enzyme is responsible for the intracellular proteolysis of insulin. Its gene IDE is located on chromosome 10, in an area with suggestive linkage to type 2 diabetes and related phenotypes. Due to the impact of genetic variants of this gene in rodents and the function of its protein product, it has been proposed as a candidate gene for type 2 diabetes. Various groups have explored the role of the common genetic variation of IDE on insulin resistance and reported associations of various single nucleotide polymorphisms (SNPs) and haplotypes on both type 2 diabetes and glycemic traits. We sought to characterize the haplotype structure of IDE in detail and replicate the association of common variants with type 2 diabetes, fasting insulin, fasting glucose, and insulin resistance. We assessed linkage disequilibrium, selected single-marker and multimarker tags, and genotyped these markers in several case-control and family-based samples totalling 4,206 Caucasian individuals. We observed no statistically significant evidence of association between single-marker or multimarker tests in IDE and type 2 diabetes. Nominally significant differences in quantitative traits are consistent with statistical noise. We conclude that common genetic variation at IDE is unlikely to confer clinically significant risk of type 2 diabetes in Caucasians.
Florez
Jose C
JC
Diabetes Unit, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. jcflorez@partners.org
Wiltshire
Steven
S
Agapakis
Christina M
CM
Burtt
Noël P
NP
de Bakker
Paul I W
PI
Almgren
Peter
P
Bengtsson Boström
Kristina
K
Tuomi
Tiinamaija
T
Gaudet
Daniel
D
Daly
Mark J
MJ
Hirschhorn
Joel N
JN
McCarthy
Mark I
MI
Altshuler
David
D
Groop
Leif
L
D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007339:Insulysin / Q000235:genetics*; D015810:Linkage Disequilibrium; D010641:Phenotype; D044465:White People
D007339:Insulysin