Is genetic susceptibility to pre-eclampsia conferred by homozygosity for the same single recessive gene in mother and fetus?

OBJECTIVE

To determine whether any simple, purely genetic mechanism can account for susceptibility to pre-eclampsia.

DESIGN

Six simple Mendelian models of inheritance were considered, and predictions concerning the incidence of pre-eclampsia in various family members of index cases were calculated for each genetic model. Data were then extracted from published family studies in which a suitable disease definition had been used, and compared to our theoretical expectations.

RESULTS

Only one of the genetic models considered, in which both mother and fetus must express the same recessive gene to confer susceptibility, was consistent with the observed incidence values for relatives of index cases. This model was also consistent with the putative association with HLA-DR4, but could not account for the comparative rarity of pre-eclampsia in parous women.

CONCLUSION

Homozygosity for a single recessive gene shared by mother and fetus, unlike five other genetic mechanisms tested, is consistent with published family studies in pre-eclampsia, and should be considered the best working hypothesis at present.