| Summary: | <p>Abstract</p> <p>Background</p> <p>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 (<it>REN</it>) and maternal angiotensinogen (<it>AGT</it>) interact to influence the risk of preeclampsia.</p> <p>Methods</p> <p>Three haplotype-tagging SNPs (htSNPs) covering <it>REN </it>(rs5705, rs1464818, and rs3795575) and another three covering <it>AGT </it>(rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal <it>AGT </it>and fetal <it>REN </it>haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal <it>AGT </it>and fetal <it>REN </it>haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal <it>AGT </it>haplotype C-T-A and tested for an effect of fetal <it>REN </it>across these strata.</p> <p>Results</p> <p>We found evidence that mothers carrying the most frequent <it>AGT </it>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 <it>AGT </it>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 <it>REN </it>haplotypes and no support for our hypothesis that an effect of <it>REN </it>depended on whether the mother carried the C-T-A haplotype of <it>AGT </it>(p = 0.33).</p> <p>Conclusion</p> <p>Our findings indicate that the mother's <it>AGT </it>haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal <it>REN </it>haplotypes.</p>
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