Abstract
The proteins cathepsin D, encoded by CTSD gene, and α2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of β-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C→T and A2M-Ile/Val A→G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI) = 1.01-3.72], and 2.07 (95% CI = 1.01-4.21) after adjustment for age, sex and APOE ε4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI = 1.13-6.34) [2.82 (95% CI = 1.12-7.17) after adjustment], and to 3.29 (95% CI = 1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk.
| Original language | English |
|---|---|
| Pages (from-to) | 187-191 |
| Number of pages | 5 |
| Journal | Journal of the Neurological Sciences |
| Volume | 247 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Sep 25 2006 |
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Keywords
- α-Macroglobulin
- Alzheimer's disease
- Cathepsin D
- Interaction
- Polymorphisms
ASJC Scopus subject areas
- Ageing
- Clinical Neurology
- Surgery
- Neuroscience(all)
- Developmental Neuroscience
- Neurology
Cite this
Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease. / Mariani, Elena; Seripa, Davide; Ingegni, Tiziana; Nocentini, Giuseppe; Mangialasche, Francesca; Ercolani, Sara; Cherubini, Antonio; Metastasio, Antonio; Pilotto, Alberto; Senin, Umberto; Mecocci, Patrizia.
In: Journal of the Neurological Sciences, Vol. 247, No. 2, 25.09.2006, p. 187-191.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease
AU - Mariani, Elena
AU - Seripa, Davide
AU - Ingegni, Tiziana
AU - Nocentini, Giuseppe
AU - Mangialasche, Francesca
AU - Ercolani, Sara
AU - Cherubini, Antonio
AU - Metastasio, Antonio
AU - Pilotto, Alberto
AU - Senin, Umberto
AU - Mecocci, Patrizia
PY - 2006/9/25
Y1 - 2006/9/25
N2 - The proteins cathepsin D, encoded by CTSD gene, and α2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of β-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C→T and A2M-Ile/Val A→G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI) = 1.01-3.72], and 2.07 (95% CI = 1.01-4.21) after adjustment for age, sex and APOE ε4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI = 1.13-6.34) [2.82 (95% CI = 1.12-7.17) after adjustment], and to 3.29 (95% CI = 1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk.
AB - The proteins cathepsin D, encoded by CTSD gene, and α2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of β-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C→T and A2M-Ile/Val A→G) have been associated with an increased risk for Alzheimer's disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI) = 1.01-3.72], and 2.07 (95% CI = 1.01-4.21) after adjustment for age, sex and APOE ε4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI = 1.13-6.34) [2.82 (95% CI = 1.12-7.17) after adjustment], and to 3.29 (95% CI = 1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk.
KW - α-Macroglobulin
KW - Alzheimer's disease
KW - Cathepsin D
KW - Interaction
KW - Polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=33748086454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748086454&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2006.05.043
DO - 10.1016/j.jns.2006.05.043
M3 - Article
VL - 247
SP - 187
EP - 191
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 2
ER -