Association of CHAT Gene Polymorphism rs3793790 and rs2177370 with Donepezil Response and the Risk of Alzheimer’s Disease Continuum

Figures & data

Figure 1 Gene frequencies of APOE and CHAT in patients with Alzheimer’s disease continuum. (A) APOE alleles frequency. (B) The rs3793790 and rs2177370 alleles frequency. (C) CHAT genotypes frequency.

Table 1 Comparisons Between Effective Group and Ineffective Group of Donepezil Response

Factors	Ineffective group(n=25)	Effective group(n=33)	P
Age^a	70.68±7.74	70.97±8.81	0.897
Gender^b			0.847
Male	12 (48.00)	15 (45.45)
Female	13 (52.00)	18 (54.55)
Baseline MMSE scores^a	19.12±4.42	22.36±4.37	0.002
Dementia severity^b			0.052
MCI	2 (8.00)	10 (30.30)
Mild AD	19 (76.00)	22 (66.67)
Moderate AD	4 (16.00)	1 (3.03)
Comorbidities^b
Hypertension	11 (44.00)	8 (24.24)	0.112
Hyperlipidemia	13 (52.00)	12 (36.36)	0.234
Diabetes	4 (16.00)	8 (24.24)	0.443
Coronary artery disease	6 (24.00)	6 (18.18)	0.588
Cerebrovascular disease	3 (12.00)	2 (6.06)	0.643
Anxiety-depression state	10 (40.00)	7 (21.21)	0.120
Family history of dementia^b	4 (16.00)	5 (15.15)	0.930
Donepezil dose^b			0.300
5mg/d	17 (68.00)	18 (54.55)
10mg/d	8 (32.00)	15 (45.45)
APOE-ε4^b	14 (56.00)	23 (69.70)	0.282
rs3793790-G^b	3 (12.00)	14 (42.42)	0.012
rs2177370-A^b	2 (8.00)	16 (48.48)	<0.001
rs3793790-G and/or rs2177370-A^b	4 (16.00)	16 (48.48)	0.010

Notes: a expressed as “”. b expressed as “n (%)”.

Abbreviations: MMSE, Mini Mental State Examination; MCI, mild cognitive impairment; AD, Alzheimer’s disease.

Table 2 Univariate Logistic Regression Analysis of Factors Associated with Donepezil Response

Factors	OR (95% CI)	P
Age	1.00 (0.94–1.07)	0.894
Gender (Ref: male)	1.11 (0.39–3.14)	0.847
Baseline MMSE scores	1.19 (1.04–1.36)	0.014
Dementia severity
MCI	Ref	0.070
Mild AD	0.23 (0.05–1.19)	0.080
Moderate AD	0.05 (0.003–0.72)	0.028
Comorbidities
Hypertension	0.41 (0.13–1.25)	0.116
Hyperlipidemia	0.53 (0.18–1.52)	0.236
Diabetes	1.68 (0.44–6.37)	0.446
Coronary artery disease	0.70 (0.20–2.52)	0.589
Cerebrovascular disease	0.47 (0.07–3.07)	0.433
Anxiety-depression state	0.40 (0.13–1.28)	0.124
Family history of dementia	0.94 (0.22–3.92)	0.930
Donepezil dose (Ref: 5mg/d)	1.77 (0.60–5.24)	0.302
APOE-ε4	1.81 (0.61–5.34)	0.285
rs3793790-G	5.40 (1.35–21.69)	0.017
rs2177370-A	10.82 (2.19–53.51)	0.003
rs3793790-G and/or rs2177370-A	4.94 (1.39–17.57)	0.014

Abbreviations: MMSE, Mini Mental State Examination; MCI, mild cognitive impairment; AD, Alzheimer’s disease; OR, odds ratio; 95% CI, 95% confidence interval.

Table 3 Multivariate Logistic Regression Analysis of Factors Associated with Donepezil Response

Factors	OR (95% CI)	P
Dementia severity^a
MCI	Ref	0.040
Mild AD	0.19 (0.04–1.06)	0.059
Moderate AD	0.03 (0.001–0.499)	0.015
rs3793790-G and/or rs2177370-A^b	6.83 (1.64–28.49)	0.008

Notes: a. Considering the association between MMSE scores and dementia severity, only dementia severity was included in multivariate logistic regression analysis. b. Considering the association between rs3793790 and rs2177370, rs3793790-G and/or rs2177370-A were included in the multivariate logistic regression analysis.

Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer’s disease; OR, odds ratio; 95% CI, 95% confidence interval.

Table 4 Comparisons the Polymorphism of APOE and CHAT Gene Between Alzheimer’s Disease Continuum Group and Control Group

Groups	Genotypes or allele (n)			χ^2	P
APOE	ε4/ε4	ε4/non-ε4	Non-ε4/non-ε4
ADC	10	76	61	12.562	0.002
Control	5	20	48
	ε4	Non-ε4
ADC	96	198		6.995	0.008
Control	30	116
CHAT-rs3793790	GG	GA	AA
ADC	10	42	95	1.526	0.483
Control	2	20	51
	G	A
ADC	62	232		1.341	0.247
Control	24	122
CHAT-rs2177370	GG	GA	AA
ADC	84	53	10	7.768	0.019
Control	55	17	1
	G	A
ADC	221	73		8.237	0.004
Control	127	19

Abbreviation: ADC, Alzheimer’s disease continuum.

Table 5 Univariate Logistic Regression Analysis of Factors Associated with Alzheimer’s Disease Continuum

Factors	OR (95% CI)	P
Age	1.06 (1.03–1.10)	<0.001
Gender (Ref: male)	0.75 (0.43–1.32)	0.315
Years of education	1.00 (0.94–1.07)	0.963
Comorbidities
Hypertension	1.29 (0.72–2.33)	0.394
Hyperlipidemia	1.31 (0.72–2.39)	0.384
Diabetes	0.99 (0.49–2.02)	0.982
Coronary artery disease	4.06 (1.37–12.06)	0.012
Cerebrovascular disease	1.32 (0.45–3.85)	0.612
Anxiety-depression state	0.68 (0.35–1.31)	0.246
Family history of dementia	0.56 (0.28–1.10)	0.090
APOE-ε4	3.07 (1.69–5.55)	<0.001
CHAT
rs3793790-G	1.27 (0.69–2.32)	0.439
rs2177370-A	2.29 (1.23–4.28)	0.009

Abbreviations: OR, odds ratio; 95% CI, 95% confidence interval.

Figure 2 Multivariate logistic regression analysis of factors associated with Alzheimer’s disease continuum. Blue: the rs2177370 and APOE gene analyses in multivariate logistic regression analysis. Red: a combination of rs2177370 and APOE gene analyses in multivariate logistic regression analysis. Black: adjusted factors in multivariate logistic regression analysis.