Background
Reference | Population (AD:control) | SNP (w.t./variant)a
Haplotype (SNP) | Results | Limitations |
---|---|---|---|---|
Arosio et al. Neurobiol. Aging 2004, 25:1009-15 [9] | Italian (65:65) | rs1800795 (G/C) | No significant association | ◈Italian only ◈One SNP only ◈Small sample size |
Licastro et al. Neurobiol. Aging 2003, 24:921-26 [8] | Italian (332:393) |
rs1800795 (G/C)
| rs1800795: CC vs. GG: OR = 1.62, 95% CI = 1.20-2.17 | ◈Italian only ◈One SNP only |
Depboylu et al. Geriatr. Cogn. Disord 2004, 17:170-73 [10] | German (113:108) | rs1800795 (G/C) | No significant association | ◈German only ◈One SNP only |
van Oijen et al. Neurosci. Lett. 2006, 402:113-17 [11] | Netherlander (483:5636) | rs1800795 (G/C) | No significant association | ◈Netherlanders only ◈One SNP only |
He et al. Neurol. Sci. 2010, 31:165-8 [12] | Chinese (318:324) |
rs1800796
(C/G)
rs13447446 (G/C) | rs1800796: GG vs. CC: OR = 0.42, 95% CI = 0.20-0.89 | ◈Chinese only ◈Not applicable for rs13447446 (No GC or CC variants) |
Wang et al. Neurosci. Lett. 2010, 482:260-3 [13] | Chinese (341:421) |
rs1800796
(C/G)
rs7802308 (A/T)
haplotype rs1800796/rs7802308
| rs1800796 (in ApoE e4 carrier): 1) CC vs. CG + GG: OR = 3.3, 95% CI = 1.64-6.67 2) A risk haplotype (CA) (OR = 2.24) 3) A protective haplotype (GA) (OR = 0.41) | ◈Chinese only ◈Significant only in ApoE e4-carrier ◈rs7802308 is a rare SNP for analysis |
Nishimura et al. Neurosci. Lett. 2004, 368:140-3 [14] | Japanese (172:163) |
rs1800796 (C/G) | No significant association | ◈Japanese only ◈One SNP only |
Methods
Study population
Dementia evaluation
SNP selection and genotyping assay
Statistical analysis
Results
Characteristics of the study population
Variables | AD N = 266 | Control N = 444 |
---|---|---|
Age (mean ± SD) | 79.8 ± 7.9* | 73.1 ± 7.1 |
Female (%) | 170 (64)* | 233 (52) |
Education (%) | ||
≦6 years | 134 (50)* | 54 (11) |
6-12 years | 90 (34) | 177 (40) |
> 12 years | 39 (15) | 214 (48) |
BMI at age 40s, kg/m2(mean ± SD) | 22.6 ± 3.1 | 22.4 ± 2.8 |
Cigarette smoking (%) | 62 (23) | 77 (17) |
Alcohol consumption (%) | 32 (12) | 50 (11) |
Type 2 DM (%) | 48 (17) | 62 (13) |
Hypertension (%) | 101 (38)* | 239 (54) |
Hyperlipidemia (%) | 49 (18)* | 135 (30) |
ApoE e4 carriers (%) | 104 (39)* | 66 (15) |
ApoE SNPs
HapMap or dbSNP | This study | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
SNP name
|
Nucleotide change
|
Location
|
rs no. |
MAF
|
Controls
|
Cases
| ||||||
CEU
|
JPT
|
CHB
|
MAF
|
HWE
|
MAF
|
HWE
| ||||||
χ
2
|
p
|
χ
2
|
p
| |||||||||
SNP1 | C→G | Promoter | rs1800796 | 0.04 | 0.14 | 0.23 | 0.26 | 0.98 | 0.32 | 0.22 | 0.36 | 0.55 |
SNP2 | A→G | Intron | rs2069837 | 0.08 | 0.10 | 0.17 | 0.19 | 2.59 | 0.11 | 0.16 | 0.04 | 0.84 |
SNP3 | T→C | Intron | rs1524107 | 0.05 | 0.18 | 0.29 | 0.27 | 1.31 | 0.25 | 0.22 | 0.22 | 0.64 |
ApoE112 | T→C | Exon | rs429358 | 0.15* | 0.01 | 0.00 | 0.08 | 0.17 | 0.68 | 0.23 | 1.24 | 0.27 |
ApoE158 | C→T | Exon | rs7412 | 0.08* | 0.05 | 0.11 | 0.08 | 1.49 | 0.22 | 0.06 | 0.001 | 0.97 |
IL-6 SNPs and AD risk
Dominant model | Additive model | ||||||
---|---|---|---|---|---|---|---|
0 copies
|
1 or 2 copies
| ||||||
Case/
control
|
AOR
|
Case/
control
|
AOR (95% CI)
|
p
|
AOR (95% CI)
|
p
| |
SNP1
| 162/245 | 1.00 | 104/196 |
0.64 (0.43-0.94)*
|
0.02
|
0.67 (0.50-0.91)*
|
0.01
|
ApoE e4 non-carriers | 100/207 | 1.00 | 61/166 |
0.56 (0.35-0.90)*
|
0.02
|
0.61 (0.42-0.90)*
|
0.01
|
ApoE e4 carriers | 61/37 | 1.00 | 43/29 | 0.82 (0.40-1.70) | 0.60 | 0.81 (0.49-1.34) | 0.28 |
SNP2
| 180/293 | 1.00 | 75/141 | 0.78 (0.51-1.19) | 0.25 | 0.80 (0.56-1.14) | 0.21 |
ApoE e4 non-carriers | 114/249 | 1.00 | 40/118 | 0.72 (0.43-1.20) | 0.21 | 0.72 (0.46-1.12) | 0.14 |
ApoE e4 carriers | 66/43 | 1.00 | 35/22 | 0.89 (0.42-1.91) | 0.77 | 0.99 (0.54-1.83) | 0.59 |
SNP3
| 163/242 | 1.00 | 102/199 |
0.60 (0.41-0.89)*
|
0.01
|
0.66 (0.49-0.90)*
|
< 0.01
|
ApoE e4 non-carriers | 101/204 | 1.00 | 60/169 |
0.55 (0.35-0.88)*
|
0.01
|
0.60 (0.41-0.89)*
|
0.01
|
ApoE e4 carriers | 61/37 | 1.00 | 42/29 | 0.73 (0.36-1.52) | 0.40 | 0.81 (0.48-1.34) | 0.23 |
IL-6 haplotypes and AD risk
Prevalence in controls, % | 2 copies | 1 or 0 copies | ||||
---|---|---|---|---|---|---|
Case/Control
|
AOR
|
Case/Control
|
AOR (95% CI)
|
p
| ||
HAP1 (CAT)a
| 73.3 | 159/244 | 1.00 | 107/200 |
0.65 (0.44-0.95)
|
0.02
|
ApoE e4 non-carriers | 99/206 | 1.00 | 62/170 |
0.57 (0.36-0.91)
|
0.02
| |
ApoE e4 carriers | 59/37 | 1.00 | 45/29 | 0.85 (0.42-1.76) | 0.67 | |
Prevalence in controls, % | 0 copies | 1 or 2 copies | ||||
Case/Control | AOR | Case/Control | AOR (95% CI) |
p
| ||
HAP2 (GGC) | 17.8 | 263/439 | 1.00 | 3/5 | 1.10 (0.16-7.58) | 0.92 |
HAP3 (GAC) | 8.1 | 260/442 | 1.00 | 6/2 | 2.56 (0.39-16.95) | 0.33 |
Effect modification by vascular risk factors
Dominant model |
p
interaction
a
| ||||
---|---|---|---|---|---|
0 copies
|
1 or 2 copies
| ||||
Case/
Control
|
AOR
|
Case/
Control
|
AOR (95% CI)
| ||
Hypertension | 266/443 |
0.41 (0.28-0.60)
| NA | ||
SNP1 | |||||
No | 96/105 | 1.00 | 69/98 | 0.64 (0.37-1.09) | 0.54 |
Yes | 66/139 | 1.00 | 35/98 |
0.53 (0.29-0.96)*
| |
SNP2 | |||||
No | 106/131 | 1.00 | 52/67 | 1.09 (0.61-1.92) |
0.03
|
Yes | 74/161 | 1.00 | 23/74 |
0.43 (0.22-0.86)*
| |
SNP3 | |||||
No | 99/102 | 1.00 | 66/100 | 0.59 (0.34-1.01) | 0.74 |
Yes | 64/139 | 1.00 | 36/99 |
0.53 (0.29-0.97)*
| |
Type 2 DM | 263/442 |
0.47 (0.30-0.74)
| NA | ||
SNP1 | |||||
No | 136/210 | 1.00 | 81/167 |
0.58 (0.38-0.90)*
| 0.48 |
Yes | 25/33 | 1.00 | 23/29 | 0.91 (0.36-1.31) | |
SNP2 | |||||
No | 146/251 | 1.00 | 61/119 | 0.77 (0.48-1.23) | 0.96 |
Yes | 33/40 | 1.00 | 14/22 | 0.78 (0.28-2.20) | |
SNP3 | |||||
No | 136/207 | 1.00 | 80/171 |
0.54 (0.35-0.84)*
| 0.39 |
Yes | 26/33 | 1.00 | 22/28 | 0.92 (0.37-2.31) |
2 copiesa
| 0 or 1 copy |
p
interaction
b
| |||
---|---|---|---|---|---|
Case/Control
|
AOR
|
Case/Control
|
AOR (95% CI)
| ||
Hypertension | |||||
No | 94/104 | 1.00 | 71/100 | 0.67 (0.39-1.15) | 0.49 |
Yes | 65/139 | 1.00 | 36/100 |
0.52 (0.29-0.95)
| |
Type 2 DM | |||||
No | 133/209 | 1.00 | 84/171 |
0.59 (0.39-0.92)
| 0.36 |
Yes | 25/33 | 1.00 | 23/29 | 0.91 (0.36-2.26) |