The L10F mutation of angiotensinogen is rare in pre-eclampsia.
BACKGROUND
A mutation in the gene for angiotensinogen, changing the leucine residue at position 10 to a phenylalanine (L10F), has been reported in a patient with proteinuric pre-eclampsia. In vitro enzymatic studies suggest this mutation would increase production of the vasoactive peptide, angiotensin II in vivo, and therefore explain the etiology of the maternal hypertension.


OBJECTIVE
To determine whether mutation of codon 10 of angiotensinogen is common in pre-eclampsia, and therefore likely to be involved in disease susceptibility.


METHODS
We collected a cohort of 32 women with 'true' pre-eclampsia. All were normotensive prior to the 20th week of pregnancy, developed blood pressures consistently above 140/90 mmHg and had proteinuria of greater than 300 mg/day during the third trimester. All had blood pressures that returned to normal within 1 month of delivery; 31 women were primigravida. Genomic DNA was isolated from their peripheral blood lymphocytes for genetic analyses.


METHODS
A polymerase chain reaction-restriction enzyme-based assay was devised to screen for mutation of codon 10 of the angiotensinogen gene. In addition, we determined the frequency of a threonine residue at position 235 in the angiotensinogen gene, given previous controversial findings of association of this polymorphism with disease.


CONCLUSIONS
We detected no mutation of codon 10 in angiotensinogen in any of the 32 women studied, indicating that this mutation is not commonly associated with proteinuric pre-eclampsia. Furthermore, there was no increased frequency of threonine 235 in the affected individuals studied compared with respective normotensive Caucasian-American and African-American populations.
Curnow
K M
KM
Baker Medical Research Institute, Melbourne, Australia. curnow@baker.edu.au
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August
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D000328:Adult; D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000235:genetics*; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy
D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D000808:Angiotensinogen