Association of Different Combinations of ALDH2 rs671, APOE rs429358, rs7412 Polymorphisms with Hypertension in Middle-Aged and Elderly People: A Case–Control Study

Figures & data

Table 1 Clinical Characteristics of Hypertensive Patients and Control Participants

	Total (n=4531)	Controls (n=1921)	Hypertensive Patients (n=2610)	P values
Age, years	66.60±12.10	65.59±12.56	67.35±11.70	<0.001
Gender
Male, n(%)	3057(67.5%)	1316(68.5%)	1741(66.7%)	0.211
Female, n(%)	1474 (32.5%)	605(31.5%)	869(33.3%)
History of smoking, n(%)	1328(29.3%)	631(32.8%)	697(26.7%)	<0.001
History of alcohol consumption, n(%)	299(6.6%)	162(8.4%)	137(5.2%)	<0.001
Hcy, μmol/L	16.70±8.09	16.04±8.07	17.18±8.08	<0.001
TG, mmol/L	1.77±1.69	1.69±1.79	1.83±1.61	0.007
TC, mmol/L	4.89±1.40	4.79±1.49	4.95±1.32	<0.001
HDL-C, mmol/L	1.26±0.39	1.25±0.40	1.27±0.38	0.070
LDL-C, mmol/L	2.73±0.98	2.68±1.03	2.77±0.94	0.001
Apo-A1, g/L	1.10±0.33	1.07±0.34	1.12±0.31	<0.001
Apo-B, g/L	0.85±0.29	0.83±0.30	0.86±0.28	<0.001

Note: Values for age expressed as mean±SD.

Abbreviations: Hcy, homocysteine; 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 Frequencies of APOE rs429358, rs7412, ALDH2 rs671 Genotypes in Hypertensive Patients and Controls

	Genotype/Allele	Controls (n=1921)	Hypertensive Patients (n=2610)	χ^2	P value
ALDH2 rs671	G/G	877(45.65%)	1246(47.74%)	2.452	0.293
	G/A	861(44.82%)	1140(43.68%)
	A/A	183(9.53%)	224(8.58%)
	G	2615(68.06%)	3632(69.58%)	2.372	0.124
	A	1227(31.94%)	1588(30.42%)
	HWE (χ^2, P), p	χ^2=1.842, P=0.175	χ^2=2.633, P=0.105
APOE rs429358	T/T	1551(80.74%)	2113(80.96%)	0.061	0.965
	T/C	352(18.32%)	474(18.16%)
	C/C	18(0.94%)	23(0.88%)
	T	3454(89.90%)	4700(90.04%)	0.046	0.832
	C	388(10.10%)	520(9.96%)
	HWE (χ^2, P), p	χ^2=0.160, P=0.689	χ^2=0.401, P=0.527
APOE rs7412	C/C	1668(86.83%)	2259(86.55%)	2.993	0.227
	C/T	247(12.86%)	333(12.76%)
	T/T	6(0.31%)	18(0.69%)
	C	3583(93.26%)	4851(92.93%)	0.368	0.558
	T	259(6.74%)	369(7.07%)
	HWE (χ^2, P)	χ^2=0.982, P=0.322	χ^2=2.182, P=0.140

Abbreviation: HWE, Hardy Weinberg Equilibrium.

Figure 1 The PCR-microarray test results of all genotypes in different polymorphisms. ALDH2 rs671 (A); APOE rs429358 and rs7412 (B).

Table 3 Comparison of Clinical Characteristics and Frequency of Gene Polymorphisms Between Hypertensive Patients and Controls in the Middle-Aged Group (30–59 Years Old) and Elderly Group (≥60 Years Old)

Clinical Characteristics	Middle-Aged Group (30–59 Years Old) (n=1285)				Elderly Group (≥60 Years Old) (n=3246)
	Total (n=1285)	Controls (n=619)	Hypertensive Patients (n=666)	P values	Total (n=3246)	Controls (n=1302)	Hypertensive Patients (n=1944)	P values
Age, years	51.60±6.02	51.16±6.41	52.02±5.60	0.011	72.54±8.11	72.45±8.20	72.60±8.06	0.608
Gender
Male, n(%)	907(70.6%)	439(70.9%)	468(70.3%)	0.807	2150(66.2%)	877(67.4%)	1273(65.5%)	0.272
Female, n(%)	378(29.4%)	180(29.1%)	198(29.7%)		1096(33.8%)	425(32.6%)	671(34.5%)
History of smoking, n(%)	423(32.9%)	214(34.6%)	209(31.4%)	0.235	905(27.9%)	417(32.0%)	488(25.1%)	<0.001
History of alcohol consumption, n(%)	97(7.5%)	59(9.5%)	38(5.7%)	0.011	202(6.2%)	103(7.9%)	99(5.1%)	0.001
Hcy, μmol/L	14.92±7.58	14.48±8.39	15.32±6.71	0.047	17.40±8.19	16.78±7.80	17.81±8.41	<0.001
TG, mmol/L	2.12±2.29	2.03±2.47	2.20±2.11	0.198	1.63±1.36	1.53±1.32	1.70±1.38	<0.001
TC, mmol/L	5.08±1.48	4.99±1.60	5.17±1.36	0.025	4.81±1.35	4.70±1.42	4.88±1.30	<0.001
HDL-C, mmol/L	1.23±0.38	1.22±0.38	1.25±0.39	0.132	1.27±0.39	1.26±0.41	1.28±0.38	0.340
LDL-C, mmol/L	2.83±1.01	2.78±1.06	2.89±0.96	0.065	2.70±0.96	2.63±1.01	2.73±0.93	0.003
Apo-A1, g/L	1.12±0.33	1.09±0.34	1.14±0.32	0.007	1.09±0.32	1.07±0.34	1.11±0.31	<0.001
Apo-B, g/L	0.87±0.30	0.85±0.31	0.90±0.29	0.005	0.84±0.28	0.82±0.29	0.85±0.27	0.001
ALDH2 rs671
G/G	617(48.0%)	286(46.2%)	331(49.7%)	0.255	1506(46.4%)	591(45.4%)	915(47.1%)	0.628
G/A	558(43.4%)	273(44.1%)	285(42.8%)		1443(44.5%)	588(45.2%)	855(44.0%)
A/A	110(8.6%)	60(9.7%)	50(7.5%)		297(9.1%)	123(9.4%)	174(9.0%)
APOE rs429358
T/T	1033(80.4%)	488(78.8%)	545(81.8%)	0.375	2631(81.1%)	1063(81.6%)	1568(80.7%)	0.723
T/C	237(18.4%)	124(20.0%)	113(17.0%)		589(18.1%)	228(17.5%)	361(18.6%)
C/C	15(1.2%)	7(1.1%)	8(1.2%)		26(0.8%)	11(0.8%)	15(0.8%)
APOE rs7412
C/C	1112(86.5%)	531(85.8%)	581(87.2%)	0.761	2815(86.7%)	1137(87.3%)	1678(86.3%)	0.075
C/T	165(12.8%)	84(13.6%)	81(12.2%)		415(12.8%)	163(12.5%)	252(13.0%)
T/T	8(0.6%)	4(0.6%)	4(0.6%)		16(0.5%)	2(0.2%)	14(0.7%)

Table 4 Association of ALDH2 rs671 and APOE rs429358, rs7412 Polymorphisms with Hypertension

SNP	Genotype	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values*
ALDH2 rs671	G/G	1.000(reference)		1.000(reference)
	G/A	0.932(0.824–1.055)	0.264	0.899(0.794–1.019)	0.097
	A/A	0.862(0.696–1.067)	0.171	0.815(0.657–1.012)	0.064
	G/A+ A/A	0.920(0.817–1.035)	0.164	0.885(0.785–0.997)	0.045
	G/G+ G/A	1.000(reference)		1.000(reference)
	A/A	0.892(0.726–1.094)	0.272	0.860(0.699–1.057)	0.151
APOE rs429358	T/T	1.000(reference)		1.000(reference)
	T/C	0.988(0.848–1.151)	0.881	0.992(0.850–1.156)	0.914
	C/C	0.938(0.504–1.744)	0.840	0.950(0.509–1.774)	0.873
	T/C+C/C	0.986(0.849–1.145)	0.853	0.990(0.851–1.150)	0.891
	T/T+T/C	1.000(reference)		1.000(reference)
	C/C	0.940(0.506–1.747)	0.845	0.952(0.510–1.775)	0.877
APOE rs7412	C/C	1.000(reference)		1.000(reference)
	C/T	0.995(0.835–1.187)	0.960	0.984(0.824–1.175)	0.861
	T/T	2.215(0.877–5.592)	0.092	2.300(0.906–5.840)	0.080
	C/T+T/T	1.024(0.861–1.219)	0.786	1.015(0.852–1.208)	0.870
	C/C+C/T	1.000(reference)		1.000(reference)
	T/T	2.216(0.878–5.594)	0.092	2.304(0.908–5.850)	0.079
Comparison of polymorphisms	rs671 G/G + rs429358 T/T	1.000(reference)		1.000(reference)
	rs671 G/G + rs429358 T/C	1.000(0.799–1.252)	1.000	1.010(0.805–1.266)	0.934
	rs671 G/G + rs429358 C/C	1.696(0.595–4.835)	0.323	1.684(0.588–4.821)	0.332
	rs671 G/A + rs429358 T/T	0.960(0.837–1.101)	0.560	0.930(0.809–1.069)	0.307
	rs671 G/A + rs429358 T/C	0.856(0.680–1.077)	0.184	0.818(0.649–1.031)	0.089
	rs671 G/A + rs429358 C/C	0.578(0.238–1.402)	0.226	0.585(0.239–1.428)	0.239
	rs671 A/A + rs429358 T/T	0.797(0.626–1.013)	0.064	0.748(0.586–0.953)	0.019
	rs671 A/A + rs429358 T/C	1.192(0.762–1.866)	0.441	1.178(0.751–1.848)	0.477
	rs671 A/A + rs429358 C/C	0.707(0.099–5.028)	0.729	0.638(0.089–4.560)	0.654
	rs671 G/G + rs7412 C/C	1.000(reference)		1.000(reference)
	rs671 G/G + rs7412 C/T	1.003(0.774–1.299)	0.985	0.983(0.758–1.276)	0.900
	rs671 G/G + rs7412 T/T	1.883(0.498–7.122)	0.351	1.708(0.448–6.512)	0.433
	rs671 G/A + rs7412 C/C	0.938(0.821–1.072)	0.347	0.904(0.790–1.034)	0.140
	rs671 G/A + rs7412 C/T	0.892(0.688–1.155)	0.385	0.846(0.651–1.097)	0.207
	rs671 G/A + rs7412 T/T	1.883(0.498–7.122)	0.351	2.125(0.556–8.116)	0.270
	rs671 A/A + rs7412 C/C	0.838(0.668–1.051)	0.126	0.785(0.625–0.987)	0.038
	rs671 A/A + rs7412 C/T	1.039(0.557–1.937)	0.905	1.034(0.552–1.935)	0.918
	rs671 A/A + rs7412 T/T	–	0.999	–	0.999

Note: *P values are estimated by logistic regression adjusted for gender, age, smoking, and drinking.

Table 5 Association of ALDH2 rs671 and APOE rs429358, rs7412 Polymorphisms with Hypertension in Middle-Aged Group and Elderly Group

		Middle-Aged Group				Elderly Group
SNP	Genotype	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values*	Univariate OR (95% CI)	P values	Multivariate OR (95% CI)	P values*
ALDH2 rs671	G/G	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	G/A	0.902(0.717–1.135)	0.378	0.868(0.689–1.095)	0.233	0.939(0.810–1.088)	0.404	0.913(0.787–1.060)	0.233
	A/A	0.720(0.479–1.082)	0.114	0.679(0.451–1.025)	0.065	0.914(0.709–1.177)	0.485	0.878(0.681–1.134)	0.319
	G/A+ A/A	0.869(0.698–1.082)	0.210	0.834(0.668–1.042)	0.110	0.935(0.812–1.076)	0.348	0.907(0.787–1.046)	0.181
	G/G+ G/A	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	A/A	0.756(0.511–1.120)	0.163	0.728(0.490–1.080)	0.115	0.942(0.739–1.201)	0.631	0.919(0.721–1.173)	0.499
APOE rs429358	T/T	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	T/C	0.816(0.615–1.083)	0.158	0.820(0.617–1.090)	0.171	1.073(0.894–1.289)	0.449	1.067(0.887–1.282)	0.492
	C/C	1.023(0.368–2.843)	0.965	1.037(0.370–2.901)	0.946	0.924(0.423–2.021)	0.844	0.913(0.416–2.001)	0.820
	T/C+C/C	0.827(0.628–1.090)	0.177	0.831(0.630–1.097)	0.192	1.067(0.891–1.277)	0.483	1.059(0.884–1.269)	0.531
	T/T+T/C	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	C/C	1.063(0.383–2.949)	0.907	1.075(0.385–3.004)	0.891	0.913(0.418–1.993)	0.819	0.902(0.412–1.976)	0.797
APOE rs7412	C/C	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	C/T	0.881(0.635–1.222)	0.449	0.874(0.629–1.215)	0.423	1.048(0.848–1.294)	0.666	1.036(0.838–1.280)	0.744
	T/T	0.914(0.227–3.673)	0.899	0.928(0.229–3.757)	0.916	4.743(1.076–20.910)	0.040	4.755(1.075–21.027)	0.040
	C/T+T/T	0.883(0.641–1.216)	0.446	0.877(0.635–1.210)	0.423	1.092(0.887–1.345)	0.406	1.081(0.877–1.332)	0.467
	C/C+C/T	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	T/T	0.929(0.231–3.731)	0.917	0.943(0.233–3.817)	0.935	4.715(1.070–20.781)	0.040	4.734(1.071–20.928)	0.040
Comparison of polymorphisms	rs671 G/G + rs429358 T/T	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	rs671 G/G + rs429358 T/C	1.056(0.698–1.598)	0.796	1.067(0.702–1.619)	0.762	0.975(0.746–1.275)	0.854	0.969(0.740–1.269)	0.819
	rs671 G/G + rs429358 C/C	3.521(0.391–31.720)	0.262	3.504(0.386–31.833)	0.265	1.288(0.386–4.302)	0.680	1.319(0.393–4.423)	0.654
	rs671 G/A + rs429358 T/T	1.028(0.797–1.327)	0.830	0.991(0.766–1.282)	0.945	0.928(0.788–1.093)	0.371	0.904(0.766–1.066)	0.231
	rs671 G/A + rs429358 T/C	0.567(0.364–0.884)	0.012	0.547(0.350–0.856)	0.008	0.992(0.754–1.305)	0.952	0.954(0.724–1.258)	0.740
	rs671 G/A + rs429358 C/C	0.587(0.164–2.105)	0.413	0.578(0.159–2.094)	0.404	0.644(0.186–2.237)	0.489	0.597(0.171–2.080)	0.418
	rs671 A/A + rs429358 T/T	0.685(0.426–1.101)	0.118	0.644(0.399–1.041)	0.072	0.824(0.622–1.091)	0.177	0.789(0.595–1.048)	0.102
	rs671 A/A + rs429358 T/C	0.880(0.421–1.839)	0.734	0.846(0.403–1.775)	0.658	1.478(0.827–2.642)	0.188	1.437(0.802–2.574)	0.223
	rs671 A/A + rs429358 C/C	-	-	-	-	0.644(0.090–4.589)	0.661	0.601(0.084–4.306)	0.612
	rs671 G/G + rs7412 C/C	1.000(reference)		1.000(reference)		1.000(reference)		1.000(reference)
	rs671 G/G + rs7412 C/T	0.686(0.427–1.103)	0.120	0.680(0.422–1.098)	0.115	1.183(0.863–1.621)	0.295	1.171(0.853–1.607)	0.328
	rs671 G/G + rs7412 T/T	0.410(0.037–4.547)	0.468	0.435(0.039–4.869)	0.500	4.646(0.570–37.871)	0.151	4.066(0.498–33.182)	0.190
	rs671 G/A + rs7412 C/C	0.858(0.670–1.097)	0.222	0.827(0.644–1.060)	0.134	0.970(0.828–1.136)	0.705	0.943(0.803–1.106)	0.470
	rs671 G/A + rs7412 C/T	0.868(0.527–1.429)	0.578	0.823(0.498–1.360)	0.447	0.893(0.659–1.209)	0.464	0.853(0.629–1.157)	0.306
	rs671 G/A + rs7412 T/T	0.410(0.037–4.547)	0.468	0.419(0.037–4.737)	0.482	4.646(0.570–37.871)	0.151	5.118(0.624–41.986)	0.128
	rs671 A/A + rs7412 C/C	0.603(0.386–0.943)	0.027	0.567(0.361–0.891)	0.014	0.928(0.711–1.210)	0.581	0.889(0.680–1.162)	0.388
	rs671 A/A + rs7412 C/T	1.054(0.387–2.872)	0.918	1.018(0.372–2.784)	0.972	1.062(0.478–2.358)	0.883	1.041(0.466–2.322)	0.922
	rs671 A/A + rs7412 T/T	-	0.999	-	0.999	-	-	-	-

Note: *P values are estimated by logistic regression adjusted for gender, age, smoking, and drinking.