Molekulargenetische Untersuchungen im Kandidatengen HADHA bei Patientinnen mit HELLP-Syndrom und deren Kindern

Hypertensive disorders in pregnancy are one of the leading causes of maternal and fetal morbidity and mortality. Especially HELLP syndrome as a subgroup of these disorders is still associated with 4% pregnancy-related death of the mother and even 60% fetal mortality. There is an intensive research for etiology and pathophysiology of these disorders in order to develop predictive and therapeutic strategies. Genetic predisposition and susceptibility genes are central questions of the recent years. The possibility of maternal and fetal susceptibility genes has to be considered. Because of a clinical association of maternal HELLP syndrome and fetal LCHAD deficiency as a special inborn error of beta-oxidation of fatty acids, the responsible genes for LCHAD deficiency called HADHA and HADHB demanded attention. Especially the frequent G1528C mutation of HADHA was found in many fetal genotypes in these cases of clinical association. HADHA and HADHB seemed to be candidate genes for HELLP syndrome. Based upon this we established an analysis of the candidate gene HADHA: The occurrence of G1528C was analyzed by PCR and RFLP in 130 mothers with HELLP syndrome, in 90 children of affected pregnancies of these mothers and in 22 fathers of affected pregnancies in cases of missing fetal DNA. Neither in this population nor in a control group of 103 women with uncomplicated pregnancies the mutation G1528C could be detected. In a further analysis using single-strand conformation polymorphism analysis (SSCP) we searched for other sequence variations in the whole gene HADHA of mothers with HELLP syndrome. SSCP screening resulted in the identification of three different sequence variations: one substitution in the 5´UTR (c.130G>T), one polymorphism in intron 15 (c.1751-25T>G) and one silent mutation in exon 18 (c.2111C>T). The study population of these analysis contained at least 100 women with HELLP syndrome for each exon and, if necessary, 109 women with uncomplicated pregnancies as a control group. Statistical analysis of each sequence variation did not show a significant difference of prevalences between women with HELLP syndrome and the control group. These results demonstrate that it is unlikely that HADHA is an important maternal susceptibility gene for HELLP syndrome in Germany.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Ahillen, Ines

Contributors dc:contributor

• Zerres, Klaus

• info:eu-repo/classification/ddc/610
• Beta-Oxidation
• HELLP-Syndrom
• Hydroxyacyl-CoA-Dehydrogenase <3->
• Medizin
• LCHAD
• HADHA
• hypertensive Schwangerschaftserkrankungen
• hypertensive disorders in pregnancy
• HELLP syndrome
• LCHAD deficiency
• inborn error of beta-oxidation of fatty acids

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113202%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50667