Abstract Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE. Objective DDAH 1415G/A 1415GA GA 1415G G rs2272592, rs2272592 rs , (rs2272592) 1151A/C 1151AC AC 1151A C rs805304 (rs805304 449G/C 449GC 449G rs805305, rs805305 (rs805305) groups Methods 20 earlyonset early onset N=57 N57 N 57 (N=57 lateonset late =49, 49 =49 =49) 102. 102 . 102) Results P=0.01. P001 P P=0.01 0 01 (P=0.01) singlelocus single locus found However GCG Conclusion rs227259 (rs2272592 rs80530 (rs80530 (rs805305 2 N=5 N5 5 (N=5 4 =4 10 P00 P=0.0 (P=0.01 rs22725 (rs227259 rs8053 (rs8053 N= (N= 1 P0 P=0. (P=0.0 rs2272 (rs22725 rs805 (rs805 P=0 (P=0. rs227 (rs2272 rs80 (rs80 P= (P=0 rs22 (rs227 rs8 (rs8 (P= rs2 (rs22 (rs (P (rs2

Resumo Objetivo Examinamos a interação dos polimorfismos nos genes heme oxigenase-1 (HMOX1) eóxido nítrico sintase (NOS3) empacientes compré-eclâmpsia (PE)bem como as capacidades de resposta à metildopa e à terapia anti-hipertensiva. Métodos Os polimorfismos nos genes HMOX1 (rs2071746, A/T) e NOS3 (rs1799983, G/T) foram genotipados usando TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, EUA), e os níveis da enzima heme oxigenase-1 (HO-1) foram medidos por enzyme-linked immunosorbent assay (ELISA). Resultados Foram encontradas interações entre os genótipos da HMOX-1 e NOS3 e responsividade à metildopa, e que pacientes genotipados como AT apresentam níveis mais baixos de proteína HO-1 em comparação com o genótipo AA. Conclusão Foram encontradas interações entre os genes HMOX-1 e NOS3 e responsividade à metildopa e que o polimorfismo localizado no gene HMOX1 afeta os níveis de enzima HO-1 na resposta à metildopa e à terapia anti-hipertensiva. Esses dados sugerem o impacto da combinação desses dois polimorfismos na resposta antihipertensiva na PE.

Abstract Objective We examined the interaction of polymorphisms in the genes heme oxygenase- 1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy. Methods The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA). Results We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA. Conclusion We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.

We investigated 50 Mulatto and 120 White Brazilians for the Y-chromosome short tandem repeat (Y-STR) markers (DYS19, DYS390, DYS391, DYS392 and DYS393) and found 79 different haplotypes in the White and 35 in the Mulatto sample. Admixture estimates based on allele frequencies showed that the admixture of the white sample was 89% European, 6% African and 5% Amerindian while the Mulatto sample was 93% European and 7% African. Results were consistent with historical records of the directional mating between European males and Amerindian or African females.