Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes

Mendes, Fernanda Santos; Luizon, Marcelo Rizzatti; Lopes, Ana Cristina dos Santos; Pereira, Daniela Alves; Evangelista, Fernanda Cristina Gontijo; Godoi, Lara Carvalho; Dusse, Luci Maria; Alpoim, Patrícia Nessralla

doi:10.61622/rbgo/2024AO19

Fernanda Santos Mendes

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0001-7717-7398

Marcelo Rizzatti Luizon

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0002-8331-3525

Ana Cristina dos Santos Lopes

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0002-1111-7509

Daniela Alves Pereira

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0001-5491-6709

Fernanda Cristina Gontijo Evangelista

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0003-4682-397X

Lara Carvalho Godoi

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0003-3556-6701

Luci Maria Dusse

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0002-7484-1684

Patrícia Nessralla Alpoim Corresponding author Patrícia Nessralla Alpoim E-mail: patnessralla@yahoo.com.br

contributed to the design of the study

were involved in the data collection

data analysis and/or interpretation

writing/substantive editing and review of the manuscript and approved the final draft of the manuscript

Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0002-3602-2645

Corresponding author Patrícia Nessralla Alpoim E-mail: patnessralla@yahoo.com.br

Associate Editor Valéria Cristina Sandrim (https://orcid.org/0000-0002-6168-7470) Universidade Estadual Paulista "Júlio de Mesquita Filho", Botucatu, SP, Brasil

Conflicts to interest: none to declare.

Parameters	Normotensive pregnant (n = 102)	Early-onset PE (n = 57)	p-value*	Late-onset PE (n = 49)	p-value*
Age (years)	24.97 ± 0.61	26.79 ± 0.95	0.096	26. 52 ± 0.97	0.167
GA (weeks)	32.80 ± 0.44	30.24 ± 0.36	0.001^a a P < 0.05 vs. normotensive pregnant.	36.24 ± 0.26	<0.001^a a P < 0.05 vs. normotensive pregnant. ,^b b P < 0.05 vs. early-onset PE
BMI (Kg/m²)	24.27 ± 0.46	24.55 ± 0.74	0.742	24. 45 ± 1.40	0.869
GWG (Kg)	10.51 ± 0.56	12.37 ± 0.94	0.080	15.22 ± 1.09	<0.001^a a P < 0.05 vs. normotensive pregnant.
SBP (mmHg)	108.0 ± 0.82	169.6 ± 2.28	<0.001^a a P < 0.05 vs. normotensive pregnant.	186.5 ± 16.75	<0.001^a a P < 0.05 vs. normotensive pregnant.
DBP (mmHg)	70.20 ± 0.70	108.4 ± 1.79	<0.001^a a P < 0.05 vs. normotensive pregnant.	124.0 ± 17.92	<0.001^a a P < 0.05 vs. normotensive pregnant.
24-h-Pr (g/24h)	ND	3.44 ± 0.45		3.62 ± 0.68

Genotype or allele	Normotensive pregnant (n = 204)	Early-onset PE (n = 124)	OR (95% CI)	p-value	Late-onset PE (n = 92)	OR (95% CI)	p-value
rs2272592 (-1415 G/A)
GG	67 (81%)	43 (77%)	1.000 (Reference)	–	39 (93%)	1.000 (Reference)	–
GA	16 (19%)	13 (23%)	1.266 (0.554-2.892)	0.671	3 (7%)	0.322 (0.088-1.176)	0.112
AA	0 (0%)	0 (0%)	–	–	0 (0%)	–	–
G	150 (90%)	99 (88%)	1.000 (Reference)	–	81 (96%)	1.000 (Reference)	–
A	16 (10%)	13 (12%)	1.231 (0.567-2.672)	0.689	3 (4%)	0.347 (0.098-1.227)	0.127
rs805304 (-1151 C/A)
CC	34 (34%)	23 (37%)	1.000 (Reference)	–	23 (50%)	1.000 (Reference)	–
CA	44 (45%)	32 (52%)	1.075 (0.534-2.161)	0.860	17 (37%)	0.571 (0.264-1.234)	0.176
AA	21 (21%)	7 (11%)	0.492 (0.180-1.348)	0.228	6 (13%)	0.422 (0.147-1.208)	0.141
CA+AA	65 (66%)	39 (63%)	0.887 (0.457-1.719)	0.737	23 (50%)	0.523 (0.256-1.066)	0.099
C	112 (57%)	78 (63%)	1.000 (Reference)	–	63 (68%)	1.000 (Reference)	–
A	86 (43%)	46 (37%)	0.768 (0.484-1.217)	0.295	29 (32%)	0.599 (0.355-1.010)	0.070
rs805305 (-449 C/G)
CC	39 (38%)	22 (36%)	1.000 (Reference)	–	22 (49%)	1.000 (Reference)	–
CG	43 (42%)	29 (48%)	1.196 (0.591-2.416)	0.720	13 (29%)	0.535 (0.238-1.206)	0.158
GG	20 (10%)	10 (16%)	0.886 (0.352-2.228)	1.000	10 (22%)	0.886 (0.352-2.228)	1.000
CG+GG	63 (52%)	39 (64%)	1.097 (0.568-2.119)	0.867	23 (51%)	0.647 (0.318-1.314)	0.276
C	121 (59%)	73 (60%)	1.000 (Reference)	–	57 (63%)	1.000 (Reference)	–
G	83 (41%)	49 (40%)	0.978 (0.619-1.546)	1.000	33 (37%)	0.844 (0.505-1.408)	0.604

Haplotypes	Normotensive pregnant (N = 204)	Early-onset PE (n = 124)	P-values	OR (95% CI)	Late-onset PE (n = 92)	P-values	OR (95% CI)
G-C-C	0.5347	0.5098	0.893	1.000 (Reference)	0.5574	0.689	1.0000 (Reference)
G-A-G	0.3024	0.2843	0.541	0.9584 (0.5566-1.6502)	0.2055	0.126	0.7200 (0.3984-1.3014)
A-A-G	0.0837	0.0593	0.676	0.7937 (0.2605-2.4180)	0.0358	0.093	0.4267 (0.1159-1.5709)
G-C-G	0.0207	0.0632	0.064	2.7106 (0.7852-9.3563)	0.1274	0.003^* * Pc < 0.01 (0.05/total number of possible haplotypes) was considered significant versus normotensive pregnant, to correct for the number of comparisons made (Bonferroni’s correction)	3.2856 (1.1145-9.6864)
G-A-C	0.0417	0.0274	0.500	0.7102 (0.1907-2.6447)	0.0739	0.384	1.4223 (0.4754-4.2547)
	^a Global-stat = 5.85076, df = 6, P-val = 0.44011				^b Global-stat = 13.232, df = 5, P-val = 0.021297^* * Pc < 0.01 (0.05/total number of possible haplotypes) was considered significant versus normotensive pregnant, to correct for the number of comparisons made (Bonferroni’s correction)

Haplotypes	Normotensive Pregnant (n = 102)	Early-onset PE (n = 57)	P-value	Late-onset PE (n = 49)	P-value
G-C-C	0.5347	0.5098	0.700	0.5574	0.803
G-A-G	0.3024	0.2843	0.690	0.0358	0.067
A-A-G	0.0837	0.0593	0.704	0.2055	0.096
G-C-G	0.0207	0.0632	0.018	0.1274	0.002*
G-A-C	0.0417	0.0274	0.604	0.0739	0.244
	^a Global-stat = 8.61623, df = 6, P-val = 0.19634			^b Global-stat = 15.31869, df = 6, P-val = 0.01792

[1] Corresponding author Patrícia Nessralla Alpoim E-mail: patnessralla@yahoo.com.br

Brasil

Brasil

Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes

Abstract

Objective:

Methods:

Results:

Conclusion: