Interação entre os genes NOS3 e HMOX1 na resposta à terapia antihipertensiva em pré-eclâmpsia

Valeria Cristina Sandrim

Department of Pharmacology, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil

Marcelo Rizzatti Luizon

Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Eliane Pilan

Department of Pharmacology, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil

Mayara Caldeira-Dias

Department of Pharmacology, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil

Fernanda Borchers Coeli-Lacchini

Department of Internal Medicine, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, SP, Brazil

Georgia Kors

Department of Pharmacology, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil

Iuly Berndt

Department of Pharmacology, Instituto de Biociências de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil

Riccardo Lacchini

Department of Psychiatric Nursing and Human Sciences, Escola de Enfermagemde Ribeirão Preto,Universidade de São Paulo, Ribeirão Preto, SP, Brazil

Ricardo Carvalho Cavalli

Department of Gynecology and Obstetrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil

Address for correspondence Valeria Cristina Sandrim, PhD, Universidade Estadual Paulista (UNESP), Departamento de Farmacologia, Instituto de Biociências de Botucatu, Distrito de Rubiao Junior, S/N, Botucatu, SP, 18618-000, Brazil (e-mail: valeria.sandrim@unesp.br).

Contributions

Sandrim VC participated in the genetic analysis, study design, was involved in the statistical analyses and in the manuscript writing. Pilan E., Caldeira-Dias M., Coeli-Lacchini F. B., Kors G., Berndt I., Lacchini R., Luizon M. R. participated in the genetic analysis, and manuscript writing and revision. Cavalli R. C. participated in the study by recruiting the patients, collecting the samples, and revising the manuscript.

Genes and polymorphisms	Genotypes and alleles	HPn (%)	PEn (%)	OR (95% CI)	p-value
NFE2L2	TT	89 (41)	76 (42)	1.00 (reference)	–
rs35652124	TC	100 (46)	81 (45)	0.933 (0.515–1.688)	0.880
T > C	CC	28 (13)	24 (13)	0.953 (0.395–2.299)	1.000
	T	278 (64)	236 (65)	1.00 (reference)	–
	C	156 (36)	126 (35)	0.957 (0.536–1.709)	1.000
HMOX1	AA	56 (26)	49 (27)	1.00 (reference)	–
rs2071746	AT	106 (49)	89 (49)	0.963 (0.493–1.879)	0.963
A > T	TT	54 (25)	43 (24)	0.924 (0.425–2.011)	0.924
	A	226 (52)	188 (52)	1.00 (reference)	–
	T	208 (48)	174 (48)	1.041 (0.597–1.813)	1.000

	Genotype or allele	Methyldopa responsiveness				Antihypertensive therapy responsiveness
	Genotype or allele	Rn (%)	NRn (%)	OR (95% CI)	p-value	Rn (%)	NRn (%)	OR (95% CI)	p-value
NFE2L2	TT	27 (48)	50 (40)	1.00 (reference)	–	48 (47)	30 (37)	1.00 (reference)	–
rs35652124	TC	23 (41)	58 (47)	1.376 (0.760–2.489)	0.365	43 (42)	38 (48)	1.452 (0.798–2.639)	0.229
T > C	CC	6 (11)	16 (13)	1.418 (0.573–3.510)	0.495	11 (11)	11 (15)	1.732 9 (0.712–4.216)	0.265
	T	76 (68)	159 (64)	1.00 (reference)	–	139 (68)	96 (61)	1.00 (reference)	–
	C	36 (32)	92 (36)	1.195 (0.665–2.148)	0.654	67 (32)	61 (39)	1.359 (0.759–2.430)	0.375
HMOX1	AA	15 (28)	33 (26)	1.00 (reference)	–	29 (28)	20 (24)	1.00 (reference)	–
rs2071746	AT	34 (61)	55 (44)	0.776 (0.401–1.503)	0.502	53 (52)	36 (45)	1.010 (0.513–1.985)	1.000
A > T	TT	6 (11)	38 (30)	2.937 (1.226–7.033)	0.020	20 (20)	25 (31)	1.808 (0.826–3.958)	0.168
	A	65 (58)	119 (47)	1.00 (reference)	–	108 (54)	76 (47)	1.00 (reference)	–
	T	47 (42)	131 (53)	1.555 (0.890–2.722)	0.156	92 (46)	85 (53)	1.324 (0.759–2.308)	0.396

Interaction models	Training score	Testing score	CVC	p-value
NOS3rs1799983	0.7220	0.7220	10/10	–
HMOX1 rs2071746; NOS3 rs1799983	0.7186	0.6898	7/10	0.0125^* * P-value after 1,000 permutations.
HMOX1 rs2071746; NOS3 rs2070744; NOS3 rs1799983	0.7183	0.6263	6/10	0.1565
NFE2L2 rs35652124; HMOX1 rs2071746; NOS3 rs2070744; NOS3 rs1799983	0.5799	0.4572	10/10	0.9420

Brasil