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 p atient with proteinuric pre-eclampsia. In vitro enzymatic studies suggest t his mutation would increase production of the vasoactive peptide, angiotens in II in vivo, and therefore explain the etiology of the maternal hypertens ion. Objective To determine whether mutation of codon 10 of angiotensinogen is c ommon in pre-eclampsia, and therefore likely to be involved in disease susc eptibility. Design We collected a cohort of 32 women with 'true' pre-eclampsia, All wer e normotensive prior to the 20th week of pregnancy, developed blood pressur es consistently above 140/90 mmHg and had proteinuria of greater than 300 m g/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 devi sed to screen far mutation of codon 10 of the angiotensinogen gene. In addi tion, we determined the frequency of a threonine residue at position 235 in the angiotensinogen gene, given previous controversial findings of associa tion of this polymorphism with disease. Conclusions We detected no mutation of codon 10 in angiotensinogen in any o f the 32 women studied, indicating that this mutation is not commonly assoc iated with proteinuric pre-eclampsia. Furthermore, there was no increased f requency of threonine 235 in the affected individuals studied compared with respective normotensive Caucasian-American and African-American population s. J Hypertens 2000, 18:173-178 (C) Lippincott Williams & Wilkins.