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Previous issue date: 2014-10-06 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / O desenvolvimento de doen?as complexas, como a pr?-ecl?mpsia, ?
determinado por fatores ambientais e gen?ticos, al?m da poss?vel intera??o entre
esses fatores. As doen?as hipertensivas da gravidez (DHGs) apresentam um
amplo espectro cl?nico, que pode variar desde pr?-ecl?mpsia leve (hipertens?o e
proteinuria) at? formas mais graves, como a ecl?mpsia (convuls?es) e s?ndrome
HELLP (hem?lise, eleva??o das enzimas hep?ticas e plaquetopenia). O espectro
cl?nico parece estar ligado a diferentes mecanismos patol?gicos. Este trabalho tem
como objetivo identificar fatores (gen?ticos e ambientais) envolvidos no
desenvolvimento das DHGs. Usando uma abordagem caso-controle, selecionamos
um total de 1498 mulheres para os estudos epidemiol?gico e gen?tico, abrangendo
755 gr?vidas normotensas (controle); 518 pr?-ecl?mpsia; 84 eclampsia e 141
HELLP. As mulheres foram genotipados para 18 marcadores distribu?dos em cinco
genes candidatos (FLT1, ACVR2A, ERAP1, ERAP2 e LNPEP). Como resultado
das an?lises dos fatores ambientais, encontramos idade materna, paridade e o
?ndice de massa corporal pr?-gestacional como importantes fatores de risco
associados ?s DHGs. As an?lises gen?ticas mostraram que os genes est?o
associados de maneira fen?tipo-espec?fica: ACVR2A com pr?-ecl?mpsia precoce
(rs1424954, p=0,002); FLT1 com s?ndrome HELLP (rs9513095, p=0,003), e ERAP1
com ecl?mpsia (rs30187, p=0,03). Nossos resultados sugerem que diferentes
mecanismos gen?ticos, juntamente com fatores ambientais espec?ficos, contribuem
na determina??o do espectro cl?nico das DHGs. Al?m disso, o refinamento
fenot?pico parece ser um passo essencial na busca por genes de doen?as
complexas / The development of complex diseases such as preeclampsia are determined by
both environmental and genetic factors, but there is also interaction among these
factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo
hypertension and proteinuria after 20th week of gestation. There is a broad spectrum
of clinical presentations related to hypertensive disorders of pregnancy (HDP) that
can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome
(Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes
might be linked to different pathological mechanisms. Our work aims to identify
factors (i.e. genes and environmental) associated with the HDP?s clinical spectrum.
Using a case-control approach, we selected a total of 1498 pregnant women for
epidemiological and genetic studies, encompassing 755 normotensive (control); 518
preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs
across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the
environmental factors, we found maternal age, parity status and pre-gestational
body mass index as important risk factors associated with disease. Genes were
associated in a phenotype-specific manner: ACVR2A with early preeclampsia
(rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and
ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic
mechanisms along with specific environmental factors might determine the clinical
spectrum of HDP. In addition, phenotype refinement seems to be an essential step
in the search for complex disease genes
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/19554 |
| Date | 06 October 2014 |
| Creators | Ferreira, Leonardo Capistrano |
| Contributors | 15603016434, http://lattes.cnpq.br/7120263570947836, Chies, Jos? Artur Bogo, 52428222015, http://lattes.cnpq.br/9325091115265469, Scortecci, Katia Castanho, 13451112825, http://lattes.cnpq.br/4808910380593455, Andrade, Lara de Melo Barbosa, 70407690425, http://lattes.cnpq.br/0327817672623352, Carvalho, Maria Goretti Freire de, 05601592420, http://lattes.cnpq.br/8934375314306198, Jer?nimo, Selma Maria Bezerra |
| Publisher | Universidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM BIOQU?MICA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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