Insulin-degrading enzyme haplotypes affect insulin levels but not dementia risk.
BACKGROUND
Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia.


METHODS
We examined the association of IDE haplotypes with dementia and insulin levels in a single well-characterized cohort of Japanese-American men born between 1900 and 1919 and followed since 1965. In 1991, a fasting insulin was obtained; dementia cases were ascertained in 1991 and 1994 in a multi-stage procedure, diagnoses were made according to international guidelines. Five single-nucleotide polymorphisms were genotyped and used for haplotype analysis in a sample of 179 Alzheimer's disease cases, 104 vascular dementia cases and 516 controls nested in the total cohort.


RESULTS
The global test for the haplotype effect on insulin levels was significant (p < 0.0001), adjusting for age, education, apolipoprotein epsilon4 status and fasting glucose.


CONCLUSIONS
There was no association of IDE haplotypes with the risk of dementia. This study suggests IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimer's.
Marlowe
Lauren
L
Laboratorie of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA.
Peila
Rita
R
Benke
Kelly Suzanne
KS
Hardy
John
J
White
Lon R
LR
Launer
Lenore J
LJ
Myers
Amanda
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007339:Insulysin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D007328:Insulin; D007339:Insulysin