Tenomodulin variants, APOE and Alzheimer's disease in a Finnish case-control cohort.
The tenomodulin gene (TNMD, locus Xq-22) encodes an angiogenesis inhibitor. It is an interesting candidate gene for Alzheimer's disease (AD), since it is expressed in brain, alterations in angiogenesis have been linked to AD and in our previous studies we have observed associations between TNMD and phenotypes, which are related to increased risk of AD. The common sequence variation in the TNMD was not associated with prevalence of AD among 526 cases and 672 controls. However, a significant interaction (p=0.002) between rs5966709 and the APOE ε4-allele status was observed in women. Among the ε4-allele carriers, the women with rs5966709-TT genotype had smaller risk for having AD than those with other genotypes (odds ratio 0.47, p=0.019, false discovery rate 10.4%). According to these results the sequence variation of TNMD is not associated with AD, but might modify the effect of APOE ε4-allele in women.
Tolppanen
Anna-Maija
AM
Department of Clinical Nutrition and Food and Health Research Centre, School of Public Health and Clinical Nutrition, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
Helisalmi
Seppo
S
Hiltunen
Mikko
M
Kolehmainen
Marjukka
M
Schwab
Ursula
U
Pirttilä
Tuula
T
Pulkkinen
Leena
L
Uusitupa
Matti
M
Soininen
Hilkka
H
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012737:Sex Factors
D053327:Apolipoprotein E4; D008565:Membrane Proteins; C422444:TNMD protein, human