E2/E3 and E3/E4 Genotypes of the Apolipoprotein E are Associated with Higher Risk of Diabetes Mellitus in Patients with Hypertension

Figures & data

Table 1 Clinical Characteristics of DM Patients and Control Participants

	Total (n=2034)	DM Patients (n=808)	Controls (n=1226)	P values
Age, years
<60, n(%)	485(23.8)	185(22.9)	300(24.5)	0.426
≥60, n(%)	1549(76.2)	623(77.1)	926(75.5)
Gender
Male, n(%)	1347(66.2)	542(67.1)	805(65.7)	0.533
Female, n(%)	687(33.8)	266(32.9)	421(34.3)
History of smoking, n(%)	534(26.3)	211(26.1)	323(26.3)	0.918
History of alcoholism, n(%)	79(3.9)	39(4.8)	40(3.3)	0.079
TG, mmHg	1.85±1.70	2.20±2.03	1.63±1.40	<0.001
TC, mmol/L	4.86±1.22	4.99±1.42	4.77±1.07	<0.001
HDL-C, mmol/L	1.26±0.37	1.22±0.37	1.29±0.37	<0.001
LDL-C, mmol/L	2.70±0.84	2.78±1.00	2.65±0.7	0.002
Apo-A1, g/L	1.12±0.31	1.09±0.30	1.13±0.32	0.001
Apo-B, g/L	0.85±0.25	0.89±0.30	0.82±0.21	<0.001

Note: Values for age expressed as mean±SD.

Abbreviations: TG, triglycerides; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; Apo-A1, apolipoprotein A1; Apo-B, apolipoprotein B.

Table 2 Distribution Frequencies of APOE Genotype and Allele in DM Patients and Controls

Variable	Genotype/Allele	DM Patients (n=808)	Controls (n=1226)	χ^2	P values
APOE genotype
	E2/E2	8(1.0%)	7(0.6%)	1.169	0.280
	E2/E3	97(12.0%)	118(9.6%)	2.919	0.088
	E2/E4	17(2.1%)	12(1.0%)	4.387	0.036
	E3/E3	544(67.3%)	903(73.7%)	9.497	0.002
	E3/E4	138(17.1%)	173(14.1%)	3.313	0.069
	E4/E4	4(0.5%)	13(1.1%)	1.878	0.171
APOE allele
	ε2	130(8.0%)	144(5.9%)	7.314	0.007
	ε3	1323(81.9%)	2097(85.5%)	9.707	0.002
	ε4	163(10.1%)	211(8.6%)	2.561	0.110
	HWE (χ^2, P)	χ^2=5.790, P=0.215	χ^2=4.090, P=0.394

Abbreviation: HWE, Hardy Weinberg Equilibrium.

Table 3 Clinical Characteristics of Subjects Stratified by APOE Genotypes and Ɛ2, Ɛ3, Ɛ4 Alleles in DM Patients

Clinical Characteristics	APOE Genotypes				APOE Alleles
	E2/E3 (n=97)	E3/E3 (n=544)	E3/E4 (n=138)	P values	ɛ2 (n=122)^a	ɛ3 (n=779)^b	ɛ4 (n=159)^c	P values
Age, years
<60, n(%)	19(19.6)	130(23.9)	31(22.5)	0.545	22(18.0)	180(23.1)	35(22.0)	0.455
≥60, n(%)	78(80.4)	414(76.1)	107(77.5)		100(82.0)	599(76.9)	124(78.0)
Gender
Male, n(%)	62(63.9)	366(67.3)	93(67.4)	0.874	80(65.6)	521(66.9)	107(67.3)	0.950
Female, n(%)	35(36.1)	178(32.7)	45(32.6)		42(34.4)	258(33.1)	52(32.7)
History of smoking, n(%)	24(24.7)	150(27.6)	33(23.9)	0.160	27(22.1)	207(26.6)	34(21.4)	0.272
History of alcoholism, n(%)	5(5.2)	28(5.1)	6(4.3)	0.985	5(4.1)	39(5.0)	6(3.8)	0.754
TG, mmol/L	2.03±1.56	2.10±1.89	2.49±2.56*	0.003	2.14±1.69	2.17±1.99	2.59±2.64	0.058
TC, mmol/L	4.83±1.37	5.00±1.39	5.08±1.57	0.681	4.87±1.37	4.99±1.42	5.04±1.50	0.602
HDL-C, mmol/L	1.25±0.39	1.23±0.35	1.14±0.41^#*	0.041	1.26±0.38	1.22±0.37	1.14±0.41^#	0.026
LDL-C, mmol/L	2.61±0.87	2.78±1.00	2.89±1.10	0.221	2.61±0.87	2.78±1.00	2.85±1.05	0.110
Apo-A1, g/L	1.09±0.29	1.10±0.29	1.03±0.31*	0.021	1.10±0.31	1.09±0.29	1.03±0.31	0.090
Apo-B, g/L	0.84±0.26	0.88±0.29	0.95±0.34^#*	0.031	0.84±0.28	0.88±0.30	0.93±0.33^#	0.047

Notes: The patients with extremely rare genotypes including E2/E2, E2/E4, E4/E4 were described but excluded from the statistical analysis. LSD and SNK test were applied to analyze the differences between each pair of groups. ^aE2/E2 plus E2/E3 plus E2/E4. ^bE2/E3 plus E3/E3 plus E3/E4. ^cE2/E4 plus E3/E4 plus E4/E4. ^#Compared with E2/E3, or compared with ɛ2, P<0.05; *Compared with E3/E3, or compared with ɛ3, P<0.05.

Table 4 Multivariate Logistic Regression of Variables Related to DM in Hypertensive Patients

Variables	Genotypes	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values
Gender (Male/Female)		1.076(0.890–1.301)	0.447	1.082(0.878–1.335)	0.459
Age (≥60/<60)		1.071(0.868–1.323)	0.522	1.050(0.847–1.301)	0.656
Smokers (Yes/No)		1.021(0.833–1.250)	0.843	0.950(0.756–1.194)	0.660
Alcoholism (Yes/No)		1.562(0.993–2.458)	0.054	1.570(0.984–2.504)	0.058
APOE genotypes
	E3/E3	1.000(reference)	–	1.000(reference)	–
	E2/E2	1.897(0.684–5.261)	0.219	1.930(0.695–5.357)	0.207
	E2/E3	1.365(1.022–1.822)	0.035	1.350(1.009–1.806)	0.043
	E3/E4	1.324(1.034–1.696)	0.026	1.325(1.034–1.699)	0.026
	E4/E4	0.511(0.166–1.574)	0.242	0.529(0.171–1.631)	0.268

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.