Effect of Apolipoprotein E ε4 Allele on the Progression of Carotid Atherosclerosis Through Apolipoprotein Levels

Figures & data

Table 1 Characteristics of the Study Population

Factors	Controls (n=399)	CAS (n=399)	P value
Age (years)	59.16±13.15	60.39±12.75	0.178 ^a
Males/females	236/163	250/149	0.310 ^b
Smoking	143(35.84%)	146(36.59%)	0.825 ^b
Drinking	75(18.80%)	104(26.07%)	0.014 ^b
Diabetes	79(19.80%)	108(27.07%)	0.015^b
Hypertension	185(46.37%)	247(61.90%)	0.000^b
TC	3.88±0.95	4.04±0.95	0.025^a
HDL	1.03±0.28	1.03±0.36	0.983^a
LDL-C	2.30±0.81	2.41±0.85	0.059^a
TG	1.49±1.21	1.77±1.05	0.001^a
Cr	64.43±28.00	64.78±22.71	0.853^a
ApoA-I	1.15±0.22	1.21±0.49	0.039^a
ApoB	0.77±0.22	0.80±0.21	0.047^a
ApoB/ApoA-I	0.69±0.33	0.69±0.21	0.746^a
ApoE	37.78±15.01	39.66±17.05	0.017^a
Lipoprotein	191.79±188.73	195.35±200.12	0.805^a
DB	4.54±3.30	4.11±1.91	0.030^a
IB	9.06±5.25	8.82±4.30	0.501^a

Note: aP values were calculated by Student’s t-tests. bP values were calculated from two-sided chi-square test.

Abbreviations: CAS, carotid atherosclerosis; TC, total cholesterol; HDL, high-density lipoproteins; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; Cr, creatinine; DB, direct bilirubin; IB, indirect bilirubin; ApoA-I, apolipoprotein A-I; ApoB, apolipoprotein B; ApoE, apolipoprotein E.

Table 2 The Distributions of Genotypes and Alleles of the ApoE Gene in the CAS Patients and Controls

Genotype, n (%)	CAS Group(n=399)	Control Group(n=399)	OR (95% CI)	P^a	χ^2	P^b
E2/E2	6(1.5%)	1(0.3%)	6.072 (0.728,50.703)	0.129	14.754	0.011
E2/E3	47(11.8%)	53(13.3%)	0.872 (0.573,1.326)	0.512
E2/E4	8(2.0%)	13(3.3%)	0.608 (0.249,1.482)	0.269
E3/E3	245(61.4%)	272(68.2%)	0.743 (0.555,0.994)	0.045
E3/E4	86(21.6%)	58(14.5%)	1.615 (1.120,2.331)	0.010
E4/E4	7(1.8%)	2(0.5%)	3.545 (0.732,17.169)	0.18
HWE	χ2 = 4.336, P = 0.362	χ2 = 9.122, P =0.058
Alleles, n (%)
E2	67(8.4%)	68(8.5%)	0.984 (0.692,1.400)	0.928	6.759	0.034
E3	623(78.1%)	655(82.1%)	0.777 (0.607,0.995)	0.045
E4	108(13.5%)	75(9.4%)	1.509 (1.104,2.062)	0.010

Notes: aP and OR (95% CI) values were calculated by logistic regression adjusted for age, gender, and traditional cardiovascular risk factors. bP values were calculated from two-sided chi-square tests or Fisher’s exact tests.

Abbreviations: CAS, carotid atherosclerosis; HWE, Hardy–Weinberg equilibrium.

Table 3 Stratified Analyses Between ApoE Polymorphism and Risk of CAS

	Age≤60				Age>60				Males					Females
Genotype, n (%)	CAS	Control	OR (95% CI)	P	CAS	Control	OR (95% CI)	P	CAS		Control	OR (95% CI)	P	CAS		Control	OR (95% CI)	P
E2/E2	2(1.0%)	1(0.5%)	2.107(0.190,23.417)	0.964	4(2.1%)	0(0.0%)	0.979(0.959,1.000)	0.124	5(2.0%)		0(0.0%)	0.980(0.963,0.998)	0.062	1(0.7%)		1(0.6%)	1.095(0.068,17.657)	0.949
E2/E3	25(12.1%)	30(13.8%)	0.856(0.485,1.512)	0.665	22(11.5%)	23(12.6%)	0.895(0.480,1.668)	0.726	27(10.8%)		29(12.3%)	0.864(0.495,1.509)	0.608	20(13.4%)		24(14.7%)	0.898(0.473,1.703)	0.742
E2/E4	3(1.4%)	6(2.8%)	0.517(0.128,2.096)	0.547	5(2.6%)	7(3.8%)	0.668(0.208,2.145)	0.496	5(2.0%)		6(2.5%)	0.782(0.236,2.598)	0.688	3(2.0%)		7(4.3%)	0.458(0.016,1.804)	0.412
E3/E3	127(61.4%)	157(72.4%)	0.607(0.403,0.913)	0.016	118(561.5%)	115(63.2%)	0.929(0.611,1.412)	0.73	155(62.0%)		163(69.1%)	0.731(0.502,1.064)	0.102	90(60.4%)		109(66.9%)	0.756(0.476,1.200)	0.235
E3/E4	46(22.2%)	22(10.1%)	2.532(1.462,4.386)	0.001	40(120.8%)	36(19.8%)	1.067(0.645,1.767)	0.8	55(22.0%)		38(16.1%)	1.470(0.929,2.324)	0.099	31(20.8%)		20(12.3%)	1.878(1.018,3.466)	0.042
E4/E4	4(1.9%)	1(0.5%)	4.256(0.472,38.399)	0.341	3(1.6%)	1(0.5%)	2.873(0.296,27.874)	0.653	3(1.2%)		0(0.0%)	0.988(0.975,1.002)	0.249	4(1.9%)		2(1.2%)	2.221(0.401,12.304)	0.600
Alleles, n (%)
E2	32(7.7%)	38(8.8%)	0.873(0.534,1.426)	0.587	35(9.1%)	30(8.2%)	1.117(0.670,1.860)	0.672	42(8.4%)		35(7.4%)	1.145(0.718,1.0827)	0.570	25(8.4%)		33(10.1%)	0.813(0.471,1.403)	0.456
E3	325(78.5%)	366(84.3%)	0.678(0.478,0.962)	0.029	298(77.6%)	289(79.4%)	0.899(0.634,1.275)	0.551	392(78.4%)		393(83.3%)	0.730(0.529,1.007)	0.055	231(77.5%)		262(80.4%)	0.842(0.573,1.238)	0.382
E4	57(13.8%)	30(6.9%)	2.150(1.351,3.421)	0.001	51(13.3%)	45(12.4%)	1.086(0.707,1.668)	0.707	66(13.2%)		44(9.3%)	1.479(0.987,2.216)	0.056	42(14.1%)		31(9.5%)	1.561(0.953,2.557)	0.075

Note: P and OR (95% CI) values were calculated by logistic regression adjusted for age, gender, and traditional cardiovascular risk factors.

Abbreviation: CAS, carotid atherosclerosis.

Table 4 Relationships Between Serum Lipid Profile and ApoE Allele in CAS Patients and Control Participants

CAS Patient								Control Participants
Factors	ε2(ε2ε2+ε2ε3)	ε3(ε3)	ε4(ε3ε4+ε4ε4)	P^a	P ^b	P^c	P ^d	ε2(ε2ε2+ε2ε3)	ε3(ε3)	ε4(ε3ε4+ε4ε4)	P^a	P ^b	P^c	P ^d
TC	3.94±0.86	4.02±0.96	4.19±0.99	0.223	0.604	0.140	0.127	3.78±1.10	3.88±0.92	4.08±1.00	0.245	0.490	0.165	0.108
HDL	1.01±0.21	1.05±0.42	1.02±0.25	0.774	0.564	0.588	0.901	1.00±0.21	1.03±0.28	1.07±0.31	0.243	0.470	0.366	0.206
LDL-C	2.34±0.73	2.40±0.85	2.50±0.92	0.468	0.613	0.326	0.253	2.18±1.04	2.29±0.76	2.50±0.84	0.131	0.375	0.104	0.051
TG	1.95±1.21	1.70±1.03	1.86±1.05	0.195	0.117	0.219	0.610	1.75±1.07	1.47±1.32	1.43±0.84	0.315	0.146	0.859	0.198
Cr	62.87±16.64	64.10±16.94	68.08±36.08	1.196	0.726	0.165	0.194	62.04±20.23	64.93±30.78	65.71±22.78	0.799	0.520	0.858	0.520
ApoA-I	1.21±0.19	1.22±0.61	1.17±0.20	0.585	0.840	0.301	0.578	1.16±0.19	1.14±0.22	1.15±0.23	0.867	0.599	0.855	0.784
ApoB	0.72±0.18	0.80±0.21	0.85±0.23	0.002	0.011	0.059	0.000	0.71±0.25	0.77±0.21	0.82±0.22	0.065	0.089	0.020	0.198
ApoB/ApoA-I	0.60±0.16	0.68±0.20	0.75±0.23	0.000	0.013	0.009	0.000	0.62±0.27	0.71±0.37	0.72±0.20	0.171	0.075	0.784	0.106
ApoE	59.12±28.90	36.54±11.28	36.10±13.09	0.000	0.000	0.813	0.000	51.93±19.61	35.39±12.52	34.69±13.70	0.000	0.009	0.747	0.058
Lipoprotein	193.74±210.20	198.50±203.57	191.00±190.73	0.951	0.876	0.761	0.937	126.67±1091.79	204.54±206.33	198.19±152.65	0.032	0.008	0.827	0.002
DB	3.82±2.06	4.24±1.89	3.94±1.86	0.223	0.149	0.209	0.712	4.52±2.38	4.43±3.21	5.03±4.44	0.488	0.851	0.437	0.232
IB	8.31±3.20	9.12±4.45	8.48±4.53	0.298	0.216	0.230	0.820	8.92±4.28	8.85±5.31	10.18±5.27	0.227	0.929	0.088	0.211

Notes: aP value shows the differences compared between groups (ε2, ε3, ε4). bP values obtained when comparing ε2 subjects with ε3 subjects. cP values obtained when comparing ε4 subjects with ε3 subjects. dP values obtained when comparing ε2 subjects with ε4 subjects.

Abbreviations: CAS, carotid atherosclerosis; TC, total cholesterol; HDL, high-density lipoproteins; LDL-C, low-density lipoprotein cholesterol,; TG, triglyceride; Cr, creatinine; DB, direct bilirubin; IB, indirect bilirubin; ApoA-I, apolipoprotein A-I; ApoB, apolipoprotein B; ApoE, apolipoprotein E.

Table 5 Logistic Regression Analysis of the Risk of CAS in Northwest of China Population

Variables	P- value	OR (95% CI)
Hypertension	0.002	1.646(1.201–2.256)
ApoA-I	0.003	5.431(1.744–16.910)
LDL-C	0.025	2.682(1.131–6.361)
TG	0.010	1.341(1.072–1.677)
ε4	0.026	1.536(1.053–2.240)

Abbreviations: CAS, carotid atherosclerosis; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride.

Table 6 Multiple Logistic Regression Analysis for CAS Patients and Control Subjects

ε4
	OR (95% CI)	P-value
Age≤60	2.136(1.241–3.676)	0.006
Age>60	1.146(0.654–2.006)	0.635
Males	1.673(1.038–2.696)	0.035
Females	1.288(0.672–2.471)	0.446