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Background  Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin ( REN ) and maternal angiotensinogen ( AGT ) interact to influence the risk of preeclampsia.    Methods  Three haplotype-tagging SNPs (htSNPs) covering  REN  (rs5705, rs1464818, and rs3795575) and another three covering  AGT  (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal  AGT  and fetal  REN  haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal  AGT  and fetal  REN  haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal  AGT  haplotype C-T-A and tested for an effect of fetal  REN  across these strata.    Results  We found evidence that mothers carrying the most frequent  AGT  haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for  AGT  haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal  REN  haplotypes and no support for our hypothesis that an effect of  REN  depended on whether the mother carried the C-T-A haplotype of  AGT  (p = 0.33).    Conclusion  Our findings indicate that the mother's  AGT  haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal  REN  haplotypes.

bmc medical genetics

Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data