Pertinence between risk of preeclampsia and the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms: an updated meta-analysis based on 73 studies

Figures & data

Figure 1. The flow chart of selection and exclusion of relevant literature.

Table 1. Characteristics of the included studies of AGT M235T.

References	Country	Race	Geography	Cases			Controls			NOS	HWEp^a
				MM	MT	TT	MM	MT	TT
Ward et al. (1993)	America	Caucasian	America	3	23	15	211	257	103	7	0.1124
Guo et al. (1997)	Australia	Caucasian	Australia	32	48	26	35	30	16	7	0.0518
Guo et al. (1997)	China	Mongoloid	East Asia	4	23	45	3	18	27	7	1
Romi et al. (1997)	Indonesia	Mixed	S and SE Asia	2	10	8	14	48	38	7	0.8519
Kobashi et al. (1999)	Japan	Mongoloid	East Asia	2	12	76	18	147	216	7	0.2645
Morgan et al. (1999)	England	Caucasian	Europe	12	21	10	22	43	19	7	0.8179
Suzuki et al. (1999)	Japan	Mongoloid	East Asia	0	5	4	14	82	184	7	0.2262
Bashford et al. (2001)	America	Mixed	America	5	28	35	1	18	21	7	0.2059
Procopciuc et al. (2002)	Rumania	Caucasian	Europe	3	9	1	3	2	1	7	0.5403
Bouba et al. (2003)	Greece	Caucasian	Europe	5	24	12	32	58	12	7	0.065
Zhang et al. (2003)	America	Caucasian	America	7	30	23	164	184	52	7	0.9723
Roberts et al. (2004)	South Africa	Negroid	Africa	3	24	177	1	52	285	8	0.392
Tempfer et al. (2004)	Australia	Caucasian	Australia	6	6	12	9	3	12	6	0.0003
Choi et al. (2004)	Korea	Mongoloid	East Asia	0	38	52	6	32	60	7	0.5381
LéVesque et al. (2004)	Canada	Caucasian	America	50	88	31	108	137	49	7	0.62
Kim et al. (2004)	Korea	Mongoloid	East Asia	13	41	33	16	42	30	7	0.8463
Hillermann et al. (2005)	South Africa	Negroid	Africa	3	10	36	2	12	31	7	0.5557
Wang et al. (2006)	America	Negroid	America	93	26	2	729	250	22	7	0.9171
Benedetto et al. (2007)	Italy	Caucasian	Europe	38	59	23	29	48	26	6	0.4954
Song et al. (2007)	China	Mongoloid	East Asia	7	23	15	13	25	7	7	0.3787
Pfab et al. (2007)	Germany	Caucasian	Europe	18	33	6	292	597	122	6	<0.0000
Huanget al. (2007)	China	Mongoloid	East Asia	13	31	14	27	50	25	7	0.846
Atsushi et al. (2008)	Japan	Mongoloid	East Asia	4	15	33	11	51	51	7	0.734
Knyrim et al. (2008)	Germany	Caucasian	Europe	19	35	13	35	48	17	7	0.9374
Jenkins et al. (2008)	America	Caucasian	America	45	77	30	80	119	39	7	0.637
Jenkins et al. (2008)	America	Negroid	America	0	4	14	8	69	125	7	0.69
Dissanayake et al. (2009)	Sri Lanka	Mixed	S and SE Asia	32	75	67	30	73	68	7	0.1829
Aggarwal et al. (2010)	India	Mixed	S and SE Asia	7	55	88	4	27	87	7	0.306
Aggarwal et al. (2011)	India	Mixed	S and SE Asia	35	116	49	18	164	18	6	<0.0000
Song et al. (2012)	China	Mongoloid	East Asia	2	12	9	16	24	10	7	0.8543
Song et al. (2013)	China	Mongoloid	East Asia	8	48	36	52	28	20	6	0.0002
Radkov et al. (2013)	Russia	Caucasian	Europe	28	53	43	24	40	8	7	0.152
Coral-Vazquez et al. (2013)	Mexico	Mixed	America	11	72	147	20	122	210	7	0.6822
Groten et al. (2013)	Germany	Caucasian	Europe	27	33	14	57	83	35	7	0.6321
Groten et al. (2013)	Ghana	Negroid	Africa	1	13	67	0	22	109	7	0.2941
Shahvaisizadeh et al. (2014)	Iran	Caucasian	Central Asia	43	71	35	31	41	28	7	0.073
Afshariani et al. (2014)	Iran	Caucasian	Central Asia	31	25	13	68	20	15	6	<0.0000
Song et al. (2015)	China	Mongoloid	East Asia	18	32	25	29	35	11	7	0.9336
Li et al. (2016)	China	Mongoloid	East Asia	9	215	87	3	90	35	6	<0.0000
Aung et al. (2017)	South Africa	Negroid	Africa	0	36	321	3	39	204	7	0.4698
Chengalvala et al. (2017)	India	Mixed	S and SE Asia	13	58	79	29	61	60	7	0.0655
Zhou (2017)	China	Mongoloid	East Asia	4	52	100	12	87	187	7	0.6419
Umida (2018)	Uzbekistan	Caucasian	Central Asia	1	10	39	9	30	71	6	0.0354
Zitouni et al. (2018)	Tunisia	Caucasian	Africa	137	109	26	176	90	12	7	0.9083
Li (2018)	China	Mongoloid	East Asia	18	96	135	30	120	197	7	0.0628
Alaee et al. (2019)	Iran	Caucasian	Central Asia	27	100	51	51	129	60	7	0.2359
Procopciuc et al. (2019)	Rumania	Caucasian	Europe	24	41	22	70	45	15	7	0.0739
Zotova et al. (2019)	Russia	Caucasian	Europe	9	14	7	10	10	10	7	0.0679
Zuo et al. (2019)	China	Mongoloid	East Asia	31	51	11	29	74	30	7	0.1931
Xiao (2019)	China	Mongoloid	East Asia	48	33	4	133	60	9	7	0.5067
Xiao (2019)	China	Mixed	East Asia	27	17	13	17	12	9	6	0.0366
Loskutova et al. (2020)	Ukraine	Caucasian	Europe	40	56	36	20	20	4	7	0.7521
Jansaka et al. (2021)	Thailand	Mixed	East Asia	0	10	51	3	32	107	7	0.7403
Liu (2021)	China	Mongoloid	East Asia	82	67	23	108	40	20	6	<0.0000
Ding et al. (2022)	China	Mongoloid	East Asia	7	65	96	9	62	133	7	0.6074

Note: S and SE Asia: south and southeast Asia.

^aFor the controls.

Table 2. Characteristics of the included studies of AGT T174M.

References	Country	Race	Geography	Cases			Controls			NOS	HWEp^a
				TT	TM	MM	TT	TM	MM
Choi et al. (2004)	Korea	Mongoloid	Asia	71	19	0	83	14	1	7	0.6402
Lévesque et al. (2004)	Canada	Caucasian	America	128	44	2	260	42	3	7	0.38
Wang et al. (2006)	America	Caucasian	America	105	14	1	856	118	2	7	0.3221
Knyrim et al. (2008)	Germany	Caucasian	Europe	56	10	1	80	16	4	6	0.0153
Jiang (2008)	China	Mongoloid	Asia	48	7	0	59	11	0	7	0.4756
Dissanayake et al. (2009)	Sri Lanka	Mixed	Asia	142	30	3	127	30	4	7	0.1832
Zhou (2017)	China	Mongoloid	Asia	133	23	0	219	62	5	7	0.8012
Li (2018)	China	Mongoloid	Asia	189	44	5	277	68	4	7	0.9395
Zitouni et al. (2018)	Tunisia	Caucasian	Africa	196	22	2	167	37	0	7	0.1543
Procopciuc et al. (2019)	Rumania	Caucasian	Europe	49	27	11	104	19	7	6	0.0001
Xiao (2019)	China	Mongoloid	Asia	70	17	0	159	43	1	7	0.2874
Xiao (2019)	China	Mixed	Asia	48	16	0	36	5	0	7	0.6776

^aFor the controls.

Table 3. Characteristics of the included studies of AT1R A1166C.

References	Country	Race	Geography	Cases			Controls			HWEp^a	NOS
				AA	AC	CC	AA	AC	CC
Bouba et al. (2003)	Greece	Caucasian	Europe	25	11	5	58	37	7	0.7414	7
Plummer et al. (2004)	UK	Caucasian	Europe	48	40	10	67	41	10	0.3094	8
Seremak-Mrozikiewicz et al. (2005)	Poland	Caucasian	Europe	23	21	3	64	46	3	0.1133	7
Song et al. (2007)	China	Mongoloid	Asia	26	11	8	25	15	5	0.2563	7
Li et al. (2007)	China	Mongoloid	Asia	109	23	1	94	10	1	0.2339	7
Benedetto et al. (2007)	Italy	Caucasian	Europe	64	46	10	53	40	10	0.5469	7
Zhu (2008)	China	Mongoloid	Asia	19	10	1	27	3	0	0.7713	7
Jiang (2008)	China	Mongoloid	Asia	45	10	0	66	4	0	0.0610	7
Akbar et al. (2009)	UK	Caucasian	Europe	22	18	7	69	42	7	0.8563	7
Akbar et al. (2009)	Pakistan	Mixed	Asia	162	25	2	254	50	4	0.3964	7
Deng (2010)	China	Mongoloid	Asia	39	11	0	94	5	1	0.0094	6
Salimi et al. (2011)	Iran	Mixed	Asia	109	15	1	118	12	2	0.0205	6
Rahimi et al. (2013)	Iran	Caucasian	Asia	129	49	3	67	21	4	0.1782	7
Kvehaugen et al. (2013)	Norway	Caucasian	Europe	588	455	99	1139	975	195	0.5008	8
Zhou et al. (2013)	Australia	Caucasian	Australia	59	50	6	525	445	98	0.7909	7
Zhou (2017)	China	Mongoloid	Asia	142	12	2	260	26	0	0.4206	7
Zhang et al. (2017)	China	Mongoloid	Asia	19	10	1	27	3	0	0.7731	7
Li (2018)	China	Mongoloid	Asia	206	28	1	306	39	2	0.5373	7
Mendelova et al. (2018)	Slovakia	Caucasian	Europe	29	17	4	20	19	3	0.5950	7
Procopciuc et al. (2019)	Rumania	Caucasian	Europe	47	29	11	94	28	8	0.0076	7
Timokhina et al. (2019)	Russia	Caucasian	Europe	29	19	3	12	13	0	0.0790	7
Azimi-Nezhad et al. (2020)	Iran	Caucasian	Asia	77	38	2	78	22	3	0.3574	7
Satra et al. (2021)	Greece	Caucasian	Europe	38	34	12	60	20	4	0.1904	7
Li (2021)	China	Mongoloid	Asia	94	25	1	139	16	0	0.7981	7

^aFor the controls.

Table 4. Characteristics of the included studies of CYP11B2 C344T.

References	Country	Race	Geography	Cases			Controls			HWE p^a	NOS
				CC	CT	TT	CC	CT	TT
Yue (2005)	China	Mongoloid	Asia	6	20	17	5	17	22	0.5431	7
Percin et al. (2006)	Turkey	Caucasian	Asia	35	74	34	34	70	43	0.5934	7
Bogacz et al. (2016)	Europe	Caucasian	Europe	14	26	19	28	53	25	0.9934	7
Aung et al. (2018)	South Africa	Negroid	Africa	16	115	226	8	67	171	0.6497	7
Procopciuc et al. (2019)	Rumania	Caucasian	Europe	22	27	38	13	34	82	0.0030	6
Azimi-Nezhad et al. (2020)	Iran	Caucasian	Asia	26	76	15	28	54	21	0.5878	7
Li (2021)	China	Mongoloid	Asia	17	68	64	6	70	79	0.0455	6

^aFor the controls.

Table 5. Overall and subgroups analysis of AGT M235T polymorphism and preeclampsia risk.

Allele model							Dominant model
AGT M235T(T vs M)							AGT M235T(MT + TT vs MM)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	55	1.31[1.17–1.45]	0.000	R	70.2	0.000	Overall①	55	1.46[1.23–1.73]	0.000	R	56.9	0.000
Overall②	46	1.28[1.14–1.44]	0.000	R	68.8	0.000	Overall②	46	1.43[1.29–1.59]	0.000	F	41.5	0.002
Race							Race
Caucasian	22	1.43[1.21–1.68]	0.000	R	69.5	0.000	Caucasian	22	1.60[1.30–1.97]	0.000	R	52.9	0.002
Mongoloid	18	1.33[1.07–1.65]	0.010	R	77.7	0.000	Mongoloid	18	1.66[1.17–2.34]	0.004	R	60.9	0.000
Mongoloid^a	14	1.21[1.09–1.36]	0.001	F	37.4	0.077	Negroid	6	0.79[0.47–1.36]	0.339	F	4.8	0.386
Negroid	6	1.18[0.88–1.62]	0.193	F	45.5	0.103	Mixed	9	0.99[0.64–1.53]	0.861	F	47.4	0.055
Mixed	9	1.08[0.88–1.33]	0.459	R	53.5	0.028
Geography							Geography
Australia	2	1.41[0.97–2.04]	0.070	F	0	0.822	Australia	2	1.77[1.03–3.04]	0.040	F	0	0.974
Africa	5	1.45[1.19–1.78]	0.000	F	30.9	0.216	Africa	5	1.57[1.14–2.17]	0.006	F	44.4	0.126
America	8	1.42[1.03–1.95]	0.033	R	80.5	0.000	America	8	1.60[0.96–2.66]	0.070	R	73.5	0.000
America†	5	1.17[1.00–1.37]	0.046	F	0	0.704	Europe	11	1.39[1.01–1.92]	0.043	R	52.3	0.021
Europe	11	1.31[1.00–1.71]	0.047	R	70	0.000	East Asia	20	1.60[1.16–2.22]	0.005	R	58.2	0.001
East Asia	20	1.32[1.08–1.82]	0.008	R	75.6	0.000	Central Asia	4	1.59[1.16–2.18]	0.004	F	28.3	0.242
East Asia^a	16	1.21[1.09–1.35]	0.000	F	33.2	0.096	S and SE Asia	5	1.01[0.52–1.95]	0.817	R	70	0.010
Central Asia	4	1.34[0.98–1.83]	0.064	R	55.4	0.081
S and SE Asia	5	1.08[0.78–1.48]	0.746	R	72.7	0.005
Recessive model							Over-dominant model
AGT M235T(TT vs MM + MT)							AGT M235T(MM + TT vs MT)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	55	1.34[1.16–1.55]	0.000	R	61.5	0.000	Overall①	55	0.96[0.85–1.08]	0.367	R	56.3	0.000
Overall②	46	1.32[1.12–1.55]	0.001	R	63.1	0.000	Overall②	46	0.97[0.89–1.05]	0.422	F	35	0.012
Race							Race
Caucasian	22	1.50[1.17–1.91]	0.001	R	58.4	0.000	Caucasian	22	0.85[0.76–0.96]	0.008	F	0.5	0.452
Mongoloid	18	1.27[0.97–1.65]	0.084	R	68.4	0.000	Mongoloid	18	0.91[0.72–1.15]	0.420	R	66.7	0.000
Negroid	6	1.38[1.04–1.82]	0.023	F	0	0.577	Negroid	6	1.37[1.07–1.76]	0.012	F	0	0.897
Mixed	9	1.21[0.85–1.72]	0.292	R	69.7	0.001	Mixed	9	1.17[0.81–1.68]	0.399	R	73.2	0.000
Geography							Geography
Australia	2	1.22[0.67–2.22]	0.509	F	0	0.683	Australia	2	0.66[0.38–1.15]	0.144	F	0	0.544
Africa	5	1.49[1.14–1.96]	0.004	F	9.3	0.353	Africa	5	1.15[0.78–1.70]	0.471	R	58.2	0.048
America	8	1.57[1.07–2.29]	0.021	R	64.8	0.006	America	8	0.99[0.83–1.17]	0.900	F	0	0.531
Europe	11	1.43[0.93–2.22]	0.105	R	62.1	0.003	Europe	11	0.96[0.79–1.17]	0.691	F	2	0.423
East Asia	20	1.27[0.99–1.62]	0.062	R	65.4	0.000	East Asia	20	0.93[0.75–1.16]	0.533	R	64.1	0.000
Central Asia	4	1.18[0.88–1.59]	0.266	F	16.5	0.309	Central Asia	4	0.82[0.63–1.07]	0.140	F	49.6	0.114
S and SE Asia	5	1.23[0.66–2.29]	0.507	R	84.1	0.000	S and SE Asia	5	1.13[0.59–2.14]	0.714	R	86.5	0.000
S and SE Asia^a	3	1.22[0.91–1.65]	0.184	F	36.5	0.206	S and SE Asia ^a	3	1.02[0.76–1.37]	0.902	F	0	0.931
Codominant model							Codominant model
AGT M235T(TT vs MM)							AGT M235T(MT vs MM)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	55	1.65[1.33–2.06]	0.000	R	57.8	0.000	Overall①	55	1.37[1.24–1.52]	0.000	F	48.9	0.000
Overall②	46	1.63[1.29–2.08]	0.000	R	56.9	0.000	Overall②	46	1.34[1.20–1.50]	0.000	F	16.2	0.175
Race							Race
Caucasian	22	1.93[1.39–2.69]	0.000	R	65.9	0.000	Caucasian	22	1.49[1.30–1.71]	0.000	F	33.4	0.065
Mongoloid	18	1.75[1.14–2.68]	0.000	R	62.4	0.000	Mongoloid	18	1.56[1.12–2.19]	0.009	R	54.2	0.003
Negroid	6	0.88[0.41–1.72]	0.601	F	9.5	0.355	Negroid	6	0.79[0.52–1.20]	0.265	F	47.7	0.053
Mixed	9	1.26[0.93–2.09]	0.234	F	18.8	0.276	Mixed	9	0.88[0.66–1.18]	0.399	F	0	0.457
Geography							Geography
Australia	2	1.70[0.87–3.33]	0.123	F	0	0.827	Australia	2	1.87[1.01–2.24]	0.045	F	0	0.568
Africa	5	1.16[0.32–4.25]	0.818	R	54.7	0.065	Africa	5	1.41[1.01–1.98]	0.044	F	43.1	0.135
America	8	2.01[0.98–4.11]	0.055	R	75.1	0.000	America	8	1.43[0.92–2.24]	0.116	R	63.0	0.008
America^a	6	1.24[0.89–1.75]	0.205	F	0	0.818	Europe	11	1.26[1.01–1.57]	0.044	F	25.1	0.205
Europe	11	1.68[0.98–2.89]	0.059	R	67.5	0.001	East Asia	20	1.52[1.11–2.09]	0.010	R	50.5	0.005
East Asia	20	1.69[1.13–2.53]	0.010	R	59.2	0.000	Central Asia	4	1.63[1.16–2.30]	0.005	F	5.8	0.364
Central Asia	4	1.46[0.99–2.15]	0.054	F	18.9	0.296	S and SE Asia	5	0.98[0.48–1.99]	0.952	R	71.1	0.008
S and SE Asia	5	1.35[0.94–1.94]	0.105	F	47.2	0.109

Notes: Numbers in bold type are significant. S and SE Asia: south and southeast Asia.

①Overall analysis.

②Overall analysis without control groups which deviation from HWE balance.

^aThe results after removed outliers using Galbraith plot when heterogeneity（I²） was >75%.

Table 6. Overall and subgroups analysis of AGT T174M polymorphism and preeclampsia risk.

Allele model							Dominant model
AGT T174M(M vs T)							AGT T174M(TM + MM vs TT)
Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ
Overall①	12	1.07[0.80–1.44]	0.654	R	69.5	0.000	Overall①	12	1.09[0.79–1.50]	0.605	R	69.4	0.000
Overall②	10	0.99[0.76–1.30]	0.957	R	56.8	0.013	Overall②	10	1.00[0.74–1.35]	0.988	R	60.5	0.007
Race							Race
Caucasian	4	1.26[0.63–2.52]	0.464	R	85.6	0	Caucasian	4	1.31[0.59–2.93]	0.506	R	86.5	0
Mongoloid	5	0.87[0.69–1.11]	0.257	F	29.5	0.225	Mongoloid	5	0.87[0.67–1.12]	0.284	F	20.9	0.281
Mixed	2	1.22[0.50–2.99]	0.664	R	61.3	0.108	Mixed	2	1.29[0.49–3.40]	0.613	R	62.8	0.101
Negroid	1	1.07[0.62–1.84]	0.802	R	NA	NA	Negroid	1	1.02[0.57–1.81]	0.949	R	NA	NA
Geography							Geography
Asia	7	0.91[0.74–1.12]	0.353	F	29.7	0.202	Asia	7	0.91[0.73–1.14]	0.425	F	26.7	0.224
Africa	1	0.63[0.37–1.06]	0.082	R	NA	NA	Africa	1	0.55[0.32–0.96]	0.036	R	NA	NA
America	2	1.45[0.84–2.51]	0.179	R	60.8	0.110	America	2	1.49[0.74–2.98]	0.265	R	72.1	0.058
Europe	2	1.44[0.39–5.22]	0.584	R	88.4	0.003	Europe	2	1.61[0.42–6.16]	0.49	R	85.9	0.008
Recessive model							Over-dominant model
AGT T174M(MM vs TT + TM)							AGT T174M(MM + TT vs TM)
Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ
Overall①	12	1.25[0.74–2.11]	0.401	F	0	0.501	Overall①	12	0.92[0.68–1.25]	0.614	R	64.3	0.001
Overall②	10	1.04[0.53–2.04]	0.912	F	0	0.631	Overall②	10	1.00[0.73–1.36]	0.991	R	60.9	0.006
Race							Race
Caucasian	4	1.77[0.79–3.96]	0.143	F	2.7	0.379	Caucasian	4	0.78[0.35–1.74]	0.547	R	84.9	0
Mongoloid	5	0.82[0.31–2.15]	0.691	F	0	0.41	Mongoloid	5	1.13[0.87–1.47]	0.349	F	4.5	0.381
Mixed	2	0.68[0.15–3.11]	0.623	R	NA	NA	Mixed	2	0.76[0.30–1.94]	0.57	R	59	0.118
Negroid	1	4.09[0.37–45.47]	0.251	R	NA	NA	Negroid	1	1.04[0.58–1.88]	0.893	R	NA	NA
Geography							Geography
Asia	7	0.78[0.35–1.76]	0.551	F	0	0.558	Asia	7	1.07[0.85–1.35]	0.547	F	16.9	0.301
Africa	1	4.68[0.22–98.06]	0.32	R	NA	NA	Africa	1	1.99[1.13–3.51]	0.017	R	NA	NA
America	2	1.66[0.39–7.15]	0.496	F	0	0.408	America	2	0.69[0.32–1.49]	0.342	R	76.3	0.040
Europe	2	1.25[0.20–7.92]	0.816	R	60.1	0.113	Europe	2	0.62[0.22–1.73]	0.360	R	72.1	0.058
Codominant model							Codominant model
AGT T174M(MM vs TT)							AGT T174M(TM vs TT)
Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I2%	PQ
Overall①	12	1.33[0.79–2.25]	0.285	F	8.3	0.366	Overall①	12	1.09[0.80–1.50]	0.591	R	66.6	0.001
Overall②	10	1.03[0.53–2.03]	0.927	F	0	0.625	Overall②	10	1.00[0.73–1.36]	0.998	R	61.1	0.006
Race							Race
Caucasian	4	2.01[0.96–4.19]	0.063	F	19.4	0.293	Caucasian	4	1.32[0.57–3.02]	0.518	R	85.9	0.000
Mongoloid	5	0.80[0.31–2.10]	0.653	F	0	0.397	Mongoloid	5	0.88[0.68–1.14]	0.334	F	8	0.361
Mixed	2	0.67[0.15–3.05]	0.606	R	NA	NA	Mixed	2	1.30[0.51–3.34]	0.580	R	59.8	0.115
Negroid	1	4.08[0.37–45.34]	0.253	R	NA	NA	Negroid	1	0.97[0.54–1.74]	0.912	R	NA	NA
Geography							Geography
Asia	7	0.76[0.34–1.72]	0.514	F	0	0.545	Asia	7	0.93[0.74–1.17]	0.520	F	18.9	0.285
Africa	1	4.26[0.20–89.40]	0.35	R	NA	NA	Africa	1	0.51[0.29–0.89]	0.019	R	NA	NA
America	2	1.85[0.43–7.97]	0.409	F	0	0.467	America	2	1.46[0.68–3.17]	0.333	R	76.1	0.041
Europe	2	1.36[0.16–11.91]	0.779	R	69.7	0.069	Europe	2	1.69[0.51–5.57]	0.388	R	78.9	0.029

Note: Numbers in bold type are significant.

①Overall analysis.

②Overall analysis without control groups which deviation from HWE balance.

Table 7. Overall and subgroups analysis of AT1R A1166C polymorphism and preeclampsia risk.

Allele model							Dominant model
AT1R A1166C(C vs A)							AT1R A1166C(AC + CC vs AA)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	24	1.29[1.10–1.53]	0.002	R	61.4	0.000	Overall①	24	1.33[1.09–1.62]	0.004	R	60.8	0.000
Overall②	21	1.23[1.04–1.45]	0.016	R	57.1	0.001	Overall②	21	1.24[1.02–1.51]	0.029	R	56.0	0.001
Race							Race
Caucasian	13	1.19[0.99–1.44]	0.069	R	62.2	0.002	Caucasian	13	1.20[0.96–1.50]	0.108	R	58	0.005
Mongoloid	9	1.64[1.29–2.08]	0.000	F	49.7	0.044	Mongoloid	9	1.94[1.25–3.00]	0.003	R	56.9	0.017
Mixed	2	0.89[0.60–1.30]	0.541	F	0	0.421	Mixed	2	0.90[0.59–1.37]	0.614	F	0	0.328
Geography							Geography
Australia	1	0.86[0.63–1.17]	0.336	R	NA	NA	Australia	1	0.92[0.62–1.35]	0.662	R	NA	NA
Europe	10	1.26[0.99–1.61]	0.061	R	68.8	0.001	Europe	10	1.23[0.92–1.65]	0.165	R	65.4	0.002
Asia	13	1.45[1.10–1.90]	0.008	R	51.1	0.017	Asia	13	1.54[1.13–2.10]	0.006	R	54.0	0.01
Recessive model							Over-dominant model
AT1R A1166C(CC vs AC + AA)							AT1R A1166C(AA + CC vs AC)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	24	1.13[0.94–1.37]	0.202	F	0	0.540	Overall①	24	0.93[0.84–1.03]	0.17	R	55.0	0.001
Overall②	21	1.11[0.91–1.35]	0.302	F	0	0.505	Overall②	21	0.96[0.87–1.07]	0.488	F	49.3	0.006
Race							Race
Caucasian	13	1.11[0.91–1.35]	0.322	F	26.0	0.182	Caucasian	13	0.99[0.89–1.11]	0.87	F	39.5	0.071
Mongoloid	9	1.85[0.85–4.01]	0.119	F	0	0.902	Mongoloid	9	0.53[0.33–0.86]	0.01	R	61.9	0.007
Mixed	2	0.70[0.17–2.82]	0.616	F	0	0.771	Mixed	2	1.08[0.70–1.67]	0.718	F	21.6	0.259
Geography							Geography
Australia	1	0.54[0.23–1.27]	0.160	R	NA	NA	Australia	1	0.93[0.63–1.37]	0.708	R	NA	NA
Europe	10	1.20[0.98–1.49]	0.081	F	14.2	0.312	Europe	10	1.03[0.91–1.16]	0.636	F	42	0.077
Asia	14	1.09[0.62–1.92]	0.767	F	0	0.799	Asia	14	0.64[0.47–0.89]	0.008	R	55.8	0.007
Codominant model							Codominant model
AT1R A1166C(CC vs AA)							AT1R A1166C(AC vs AA)
Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ	Subgroup	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Overall①	24	1.13[0.93–1.38]	0.211	F	11.7	0.301	Overall①	24	1.09[0.98–1.21]	0.104	R	57.9	0.000
Overall②	21	1.10[0.90–1.34]	0.361	F	10.5	0.324	Overall②	21	1.21[0.99–1.47]	0.063	R	52.3	0.003
Race							Race
Caucasian	13	1.10[0.90–1.35]	0.340	F	40.5	0.064	Caucasian	13	1.02[0.91–1.15]	0.707	F	49.2	0.023
Mongoloid	9	1.90[0.87–4.17]	0.108	F	0	0.881	Mongoloid	9	1.91[1.19–3.07]	0.008	R	60.7	0.009
Mixed	2	0.69[0.17–2.79]	0.604	F	0	0.806	Mixed	2	0.92[0.60–1.42]	0.703	F	20.2	0.263
Geography							Geography
Australia	1	0.54[0.23–1.30]	0.170	R	NA	NA	Australia	1	1.00[0.67–1.49]	0.999	R	NA	NA
Europe	10	1.20[0.97–1.49]	0.096	F	40.2	0.090	Europe	10	1.14[0.86–1.50]	0.354	R	55.3	0.017
Asia	14	1.12[0.63–1.99]	0.695	F	0	0.806	Asia	14	1.56[1.13–2.16]	0.007	R	55.3

Note: Numbers in bold type are significant.

①Overall analysis.

②Overall analysis without control groups which deviation from HWE balance.

Table 8. Analysis of CYP11B2 C344T polymorphism and preeclampsia risk.

Genetic model	N	OR[95%CI]	Por	Effect model	I^2%	PQ
Allele (T vs C)	7	0.79[0.63–0.98]	0.032	R	55.4	0.036
Dominant (TT + CT vs CC)	7	0.73[0.48–1.12]	0.156	R	52.9	0.048
Recessive (TT vs TT + CT)	7	0.72[0.59–0.88]	0.001	F	23.8	0.247
Over-dominant(TT + CC vs CT)	7	0.83[0.69–1.01]	0.061	F	0	0.693
Codominant(TT vs CC)	7	0.61[0.45–0.84]	0.003	F	46.5	0.082
Codominant(CT vs CC)	7	0.88[0.66–1.18]	0.400	F	31.4	0.188

Note: Numbers in bold type are significant.

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