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.
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