| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-125 |
Sentence |
denotes |
The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project. |
| T2 |
126-137 |
Sentence |
denotes |
BACKGROUND: |
| T3 |
138-243 |
Sentence |
denotes |
The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). |
| T4 |
244-327 |
Sentence |
denotes |
Dopamine β-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. |
| T5 |
328-521 |
Sentence |
denotes |
Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. |
| T6 |
522-698 |
Sentence |
denotes |
We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls. |
| T7 |
699-707 |
Sentence |
denotes |
METHODS: |
| T8 |
708-804 |
Sentence |
denotes |
We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. |
| T9 |
805-927 |
Sentence |
denotes |
We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD. |
| T10 |
928-936 |
Sentence |
denotes |
RESULTS: |
| T11 |
937-1051 |
Sentence |
denotes |
We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: |
| T12 |
1052-1073 |
Sentence |
denotes |
1.06-1.4, p = 0.005). |
| T13 |
1074-1171 |
Sentence |
denotes |
This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). |
| T14 |
1172-1319 |
Sentence |
denotes |
We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). |
| T15 |
1320-1391 |
Sentence |
denotes |
All these results were consistent between North Europe and North Spain. |
| T16 |
1392-1404 |
Sentence |
denotes |
CONCLUSIONS: |
| T17 |
1405-1540 |
Sentence |
denotes |
Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. |
| T18 |
1541-1688 |
Sentence |
denotes |
Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. |
| T19 |
1689-1787 |
Sentence |
denotes |
We suggest that such misregulation is the predominant mechanism of the association we report here. |