IS ANGIOTENSINOGEN A GOOD CANDIDATE GENE FOR PREECLAMPSIA

Objective: To test the hypothesis that variants in the angiotensinogen gene are a major genetic cause of preeclampsia (PE). Methods: Ten fam ilies with a high incidence of PE were typed for alleles at a microsat ellite repeat within the angiotensinogen gene (AGT). Logarithm of odds (LODs) scores were used to examine for cosegregation of AGT alleles w ith the disease under several models of inheritance. Both recessive an d dominant modes of inheritance with penetrances ranging from 0.9 to 0 .5 were considered for a range of disease gene frequencies. A model-in dependent analysis, affected pedigree member method (AFFPED), was also used. Results: There was no indication of cosegregation between preec lampsia and angiotensinogen alleles under any model. Under most domina nt models the preeclampsia gene was excluded from a 5 centimorgan regi on around angiotensinogen (LOD < -2). AFFPED also does not support clo se linkage of AGT and the preeclampsia gene. Conclusions: Variants at the angiotensinogen gene are not responsible for the preeclampsia in t hese families, We are unable to verify the reports of two groups sugge sting that susceptibility to preeclampsia is correlated with variation at the angiotensinogen locus. Distinguishing preeclampsia from other hypertensive disorders of pregnancy has long been a difficult problem, and still remains to be solved. Raised blood pressure is almost certa inly a secondary event in the PE causal chain. The pathophysiology of preeclampsia suggests that genes involved in specifying products which affect the interaction of trophoblast and decidua are better candidat es for the origin of the fundamental lesion than are genes involved in controlling blood pressure.