Association between genetic polymorphisms of leptin receptor and preeclampsia in Chinese women

Figures & data

Table 1. Clinical, metabolic, and oxidative stress parameters of patients with PE and control women.

	Controls (n = 1295)	PE (n = 322)	p	p^a
Clinical characteristics
Age (years)	34.28 ± 4.51	31.24 ± 6.38	<.001
Pre-pregnancy BMI (kg/m^2)	21.24 ± 2.68	22.56 ± 3.49	<.001
Delivery BMI (kg/m^2)	26.60 ± 2.80	28.08 ± 3.73	<.001
SBP (mmHg)	114.96 ± 10.00	154.40 ± 20.63	<.001	<.001
DBP (mmHg)	72.60 ± 8.04	99.31 ± 14.68	<.001	<.001
Gestational age (weeks)	39.13 ± 1.13	36.02 ± 3.29	<.001	<.001
Neonatal birth height (cm)	49.85 ± 1.92	45.65 ± 5.92	<.001	<.001
Neonatal birth weight (g)	3374.81 ± 376.88	2636.98 ± 832.09	<.001	<.001
Neonatal PI (g/cm^3)	2.73 ± 0.24	2.62 ± 0.66	.086	<.001
Metabolic parameters*
TG (mmol/L)	3.63 ± 1.41	4.42 ± 2.00	<.001	<.001
TC (mmol/L)	6.02 ± 1.10	6.27 ± 1.82	.050	<.001
HDL-C (mmol/L)	1.97 ± 0.43	1.62 ± 0.59	<.001	<.001
LDL-C (mmol/L)	3.15 ± 0.99	3.19 ± 1.20	.697	.115
TG/HDL-C	1.94 ± 0.90	3.04 ± 1.72	<.001	<.001
Non-HDL-C (mmol/L)	4.06 ± 0.95	4.62 ± 1.40	<.001	<.001
AI	2.15 ± 0.66	3.15 ± 1.37	<.001	<.001
ApoA1 (g/L)	2.36 ± 0.44	2.11 ± 0.58	<.001	<.001
ApoB (g/L)	1.15 ± 0.26	1.32 ± 0.39	<.001	<.001
ApoB/apoA1	0.50 ± 0.15	0.66 ± 0.27	<.001	<.001
Oxidative stress parameters**
TOS (μmol H2O2 Equiv./L)	21.14 ± 7.06	30.57 ± 13.79	<.001	<.001
TAC (mmol trolox equiv./L)	1.10 ± 0.19	1.07 ± 0.21	.166	.262
OSI	19.56 ± 7.38	26.44 ± 13.45	<.001	<.001
MDA (nmol/mL)	5.36 ± 1.22	5.61 ± 2.34	.245	.015

BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; PI: ponderal index; TG: triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; AI: atherosclerosis index; ApoA1: apolipoprotein A1; ApoB: apolipoprotein B; TOS: total oxidant status; TAC: total antioxidant capacity; MDA: malondialdehyde; OSI: oxidative stress index.

* Controls (n = 1059), PE (n = 240).

** Controls (n = 806), PE (n = 148).

Values are presented as mean ± SD. ^aAll comparisons of parameters were corrected for differences in age and delivery BMI between the two groups, except for the parameters of age and BMI.

Table 2. Association of LEPR A233G and A668G genetic variations with the risk of PE using different genetic models.

	Controls (n = 1295)	PE (n = 322)	χ^2	p	pFDR	Statistical power	Prior probability*
							.25	.1	.01	.001
A233G
Genotype
GG	828 (63.9%)	230 (71.4%)
AG	421 (32.5%)	88 (27.3%)
AA	46 (3.6%)	4 (1.3%)	8.860	.012	.024	.764	.045	.124	.609	.940
pHWE	.702	.383
Dominant
GG	828 (63.9%)	230 (71.4%)
AA + AG	467 (36.1%)	92 (28.6%)	6.396	.011^a	.011	.715	.044	.122	.604	.939
Recessive
AG + GG	1249 (96.4%)	318 (98.8%)
AA	46 (3.6%)	4 (1.2%)	4.592	.032^b	.064	.572	.144	.335	.847	.982
Allele
G	2077 (80.2%)	548 (85.1%)
A	513 (19.8%)	96 (14.9%)	8.102	.004^c	.008	.521	.022	.065	.431	.885
A668G
Genotype
GG	976 (75.4%)	265 (82.3%)
AG	305 (23.5%)	56 (17.4%)
AA	14 (1.1%)	1 (0.3%)		.020**	.020	.700	.079	.205	.739	.966
pHWE	.185	.548
Dominant
GG	976 (75.4%)	265 (82.3%)
AA + AG	319 (24.6%)	57 (17.7%)	6.942	.008^d	.016	.750	.031	.088	.514	.914
Recessive
AG + GG	1281 (98.9%)	321 (99.7%)
AA	14 (1.1%)	1 (0.3%)		.329**	.329	.252	.797	.922	.992	.999
Allele
G	2257 (87.1%)	586 (91.0%)
A	333 (12.9%)	58 (9.0%)	7.196	.007^e	.007	.475	.042	.117	.593	.936

p_HWE: p value of the Hardy–Weinberg equilibrium test; p_FDR: adjusted p value of false discovery rate (FDR).

Genotype and allele data are presented as number (%) of patients or controls.

* The false positive report probability (FPRP) value based on different prior probability.

** Since one cell has expected count less than 5, Fisher’s exact test was used.

^a Odds ratio (OR) = 0.709, 95% confidence interval (CI): 0.543–0.926.

^b OR = 0.342, 95% CI: 0.122–0.956.

^c OR = 0.709, 95% CI: 0.559–0.899.

^d OR = 0.658, 95% CI: 0.481–0.900.

^e OR = 0.671, 95% CI: 0.500–0.899.

Table 3. Frequencies of combined genotypes of LEPR A223G and LEPR A668G in patients with PE and control women.

Genotype combinations	Controls (n = 1295)	PE (n = 322)	OR	95% CI	p
LEPR A668G/LEPR A223G^a
GG/GG	783 (60.5%)	215 (66.8%)	1.000
GG/AG + AA	193 (14.9%)	50 (15.5%)	0.884	0.600–1.302	.533
AG + AA/GG	45 (3.5%)	15 (4.7%)	1.136	0.571–2.260	.717
AG + AA/AG + AA	274 (21.2%)	42 (13.0%)	0.558	0.374–0.833	.004

Data on genotype combinations are presented as number (%) of patients or controls.

^a Chi-squared test: χ² = 11.392, p = .010. OR and 95% CI were calculated using a multinomial logistic regression model, with age and delivery BMI as covariates and the GG/GG combined genotypes as the reference category.

Table 4. Clinical, metabolic, and oxidative stress parameters according to LEPR A223G genotypes in patients with PE and control women.

	Control group		PE group
	GG (n = 828)	AG + AA (n = 421 + 46)	GG (n = 230)	AG + AA (n = 88 + 4)
Clinical characteristics
Age (years)	34.35 ± 4.39	34.16 ± 4.72	31.18 ± 6.46	31.39 ± 6.20
Pre-pregnancy BMI (kg/m^2)	21.26 ± 2.56	21.20 ± 2.88	22.76 ± 3.57	22.03 ± 3.25
Delivery BMI (kg/m^2)	26.56 ± 2.76	26.67 ± 2.86	28.10 ± 3.42	28.02 ± 4.40
SBP (mmHg)	114.90 ± 10.14	115.08 ± 9.88	153.86 ± 20.28	155.67 ± 21.50
DBP (mmHg)	72.39 ± 8.18	72.92 ± 7.77	98.21 ± 13.99	102.00 ± 16.00^b
Gestational age (weeks)	39.14 ± 1.16	39.12 ± 1.07	36.18 ± 3.20	35.64 ± 3.51
Neonatal birth height (cm)	49.75 ± 1.68	50.01 ± 2.28^a	45.94 ± 5.41	44.82 ± 7.27
Neonatal birth weight (g)	3372.31 ± 363.90	3379.19 ± 399.04	2663.62 ± 794.43	2559.69 ± 935.64
Neonatal PI (g/cm^3)	2.74 ± 0.23	2.72 ± 0.27	2.59 ± 0.68	2.72 ± 0.57
Metabolic parameters*
TG (mmol/L)	3.65 ± 1.46	3.58 ± 1.30	4.50 ± 1.99	4.20 ± 2.01
TC (mmol/L)	6.02 ± 1.09	6.01 ± 1.11	6.19 ± 1.79	6.50 ± 1.91
HDL-C (mmol/L)	1.96 ± 0.43	1.98 ± 0.41	1.57 ± 0.58	1.74 ± 0.60
LDL-C (mmol/L)	3.15 ± 1.03	3.16 ± 0.92	3.09 ± 1.11	3.45 ± 1.36^b
TG/HDL-C	1.96 ± 0.95	1.89 ± 0.79	3.15 ± 1.65	2.77 ± 1.90
Non-HDL-C (mmol/L)	4.06 ± 0.95	4.06 ± 0.94	4.54 ± 1.33	4.83 ± 1.55
AI	2.16 ± 0.69	2.12 ± 0.61	3.20 ± 1.37	3.03 ± 1.38
ApoA1 (g/L)	2.36 ± 0.41	2.36 ± 0.48	2.09 ± 0.57	2.15 ± 0.59
ApoB (g/L)	1.14 ± 0.26	1.15 ± 0.27	1.28 ± 0.34	1.41 ± 0.48^b
ApoB/apoA1	0.50 ± 0.15	0.51 ± 0.15	0.65 ± 0.25	0.69 ± 0.30
Oxidative stress parameters**
TOS (μmol H2O2 equiv./L)	20.98 ± 6.96	21.45 ± 7.27	31.94 ± 14.35	26.30 ± 11.20
TAC (mmol trolox equiv./L)	1.10 ± 0.19	1.10 ± 0.20	1.05 ± 0.20	1.14 ± 0.23^b
OSI	19.39 ± 7.25	19.90 ± 7.64	28.48 ± 14.32	20.19 ± 7.74^b
MDA (nmol/mL)	5.35 ± 1.23	5.40 ± 1.20	5.42 ± 2.23	6.11 ± 2.58

BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; PI: ponderal index; TG: triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; AI: atherosclerosis index; ApoA1: apolipoprotein A1; ApoB: apolipoprotein B; TOS: total oxidant status; TAC: total antioxidant capacity; MDA: malondialdehyde; OSI: oxidative stress index.

Values are presented as mean ± SD. All comparisons of parameters were corrected for differences in age and delivery BMI between the two subgroups, except for the parameters of age and BMI.

* Controls (GG = 710, AG + AA = 312 + 37); PE (GG = 172, AG + AA = 64 + 4).

** Controls (GG = 540, AG + AA = 236 + 30); PE (GG = 107, AG + AA = 38 + 3).

^a p < .05: compared with the GG genotype subgroup in the control group.

^b p < .05: compared with the GG genotype subgroup in the preeclampsia group.

Table 5. Clinical, metabolic, and oxidative stress parameters according to LEPR A668G genotypes in patients with PE and control women.

	Control group		PE group
	GG (n = 976)	AG + AA (n = 305 + 14)	GG (n = 265)	AG + AA (n = 56 + 1)
Clinical characteristics
Age (years)	34.26 ± 4.46	34.34 ± 4.67	31.17 ± 6.14	31.58 ± 7.51
Pre-pregnancy BMI (kg/m^2)	21.28 ± 2.60	21.11 ± 3.03	22.77 ± 3.60	21.66 ± 2.71
Delivery BMI (kg/m^2)	26.61 ± 2.76	26.57 ± 2.90	28.02 ± 3.71	28.36 ± 3.83
SBP (mmHg)	114.84 ± 10.08	115.33 ± 9.94	155.71 ± 19.70	157.69 ± 24.61
DBP (mmHg)	72.53 ± 8.20	72.75 ± 7.54	98.72 ± 14.09	102.19 ± 17.12
Gestational age (weeks)	39.14 ± 1.12	39.12 ± 1.14	36.10 ± 3.17	35.67 ± 3.86
Neonatal birth height (cm)	49.81 ± 1.77	49.96 ± 2.31	45.98 ± 5.31	44.00 ± 8.37
Neonatal birth weight (g)	3368.35 ± 365.66	3394.04 ± 408.57	2647.72 ± 782.36	2585.39 ± 1048.71
Neonatal PI (g/cm^3)	2.73 ± 0.24	2.74 ± 0.26	2.60 ± 0.65	2.74 ± 0.71
Metabolic parameters*
TG (mmol/L)	3.67 ± 1.45	3.48 ± 1.26	4.48 ± 2.02	4.07 ± 1.88
TC (mmol/L)	6.05 ± 1.08	5.89 ± 1.13	6.21 ± 1.80	6.62 ± 1.94
HDL-C (mmol/L)	1.97 ± 0.42	1.96 ± 0.44	1.58 ± 0.58	1.81 ± 0.57^a
LDL-C (mmol/L)	3.18 ± 1.01	3.07 ± 0.90	3.16 ± 1.18	3.37 ± 1.26
TG/HDL-C	1.96 ± 0.93	1.87 ± 0.76	3.16 ± 1.78	2.41 ± 1.26
Non-HDL-C (mmol/L)	4.08 ± 0.94	3.97 ± 0.95	4.58 ± 1.35	4.80 ± 1.63
AI	2.16 ± 0.67	2.11 ± 0.64	3.22 ± 1.43	2.78 ± 0.96
ApoA1 (g/L)	2.36 ± 0.41	2.36 ± 0.53	2.12 ± 0.59	2.07 ± 0.67
ApoB (g/L)	1.15 ± 0.26	1.13 ± 0.27	1.32 ± 0.38	1.33 ± 0.42
ApoB/apoA1	0.50 ± 0.15	0.50 ± 0.16	0.66 ± 0.27	0.68 ± 0.26
Oxidative stress parameters**
TOS (μmol H2O2 equiv./L)	21.11 ± 7.07	21.24 ± 7.06	30.23 ± 14.14	32.62 ± 11.93
TAC (mmol trolox equiv./L)	1.10 ± 0.20	1.11 ± 0.19	1.07 ± 0.21	1.11 ± 0.24
OSI	19.60 ± 7.39	19.41 ± 7.36	26.68 ± 14.25	25.00 ± 7.48
MDA (nmol/mL)	5.36 ± 1.21	5.39 ± 1.25	5.55 ± 2.41	5.95 ± 1.91

BMI: body mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; PI: ponderal index; TG: triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; AI: atherosclerosis index; ApoA1: apolipoprotein A1; ApoB: apolipoprotein B; TOS: total oxidant status; TAC: total antioxidant capacity; MDA: malondialdehyde; OSI: oxidative stress index.

Values are presented as mean ± SD. All comparisons of parameters were corrected for differences in age and delivery BMI between the two subgroups, except for the parameters of age and BMI.

* Controls (GG = 823, AG + AA = 227 + 9); PE (GG = 198, AG + AA = 42 + 0).

** Controls (GG = 628, AG + AA = 168 + 10); PE (GG = 123, AG + AA = 25 + 0).

^a p = .045: compared with the GG genotype subgroup in the preeclampsia group.

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors.