Abstract
BackgroundPreeclampsia 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.MethodsThree 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.ResultsWe 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).ConclusionOur findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.
Highlights
Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world
One-hundred and two mother-father-child triads of preeclamptic pregnancies were genotyped for three haplotype-tagging SNPs (htSNPs) covering REN [rs5705 (A/c), rs1464816 (G/t), rs3795575 (C/t); Figure 1A] and three additional htSNPs covering AGT [rs2148582 (C/t), rs2478545 (c/T), rs943580 (A/g); Figure 1B]
relative risks (RR) estimates with 95% confidence intervals (CI) and the corresponding pvalues are presented in Tables 2 and 3
Summary
Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Recent epidemiological studies have demonstrated that the risk of preeclampsia is determined by maternal predisposition, and by a fetal contribution inherited from the father. Pregnant women whose partner had fathered a preeclamptic pregnancy with another woman were nearly twice as likely to have preeclampsia [4]. In studies of the risk of preeclampsia across generations, partners of men who were born to a preeclamptic pregnancy had increased risk of developing preeclampsia [5,6]. Despite evidence for both maternal and fetal genetic contributions to the risk of preeclampsia, most published reports are based on the case-control design
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