Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway.
BMC Med Genet. 2010 Jun 10;11:90. doi: 10.1186/1471-2350-11-90.
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.
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.
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).
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.
子痫前期是一种影响西方世界约 3%孕妇的衰弱性疾病。虽然尚无定论，但目前的证据表明肾素-血管紧张素系统可能与高血压有关。因此，我们的目的是确定胎盘肾素 (REN) 和母体血管紧张素原 (AGT) 的基因是否相互作用，从而影响子痫前期的风险。
在 99 个子痫前期妊娠的母婴-父-子三联体中，对 REN(rs5705、rs1464818 和 rs3795575)和 AGT(rs2148582、rs2478545 和 rs943580)的三个单倍型标记 SNP(htSNP)进行了基因分型。我们使用 HAPLIN 估计了母体 AGT 和胎儿 REN 单倍型赋予的相对风险 (RR)，HAPLIN 是一种专门用于检测三联体中多标记传递扭曲的统计软件。为了评估母体 AGT 和胎儿 REN 单倍型的综合效应，首先根据母体 AGT 单倍型 C-T-A 的存在/缺失将子痫前期三联体分层，并在这些分层中测试胎儿 REN 的效应。
我们发现有证据表明，携带最常见 AGT 单倍型 C-T-A 的母亲子痫前期的风险降低 (杂合子的 RR 为 0.4，95%CI = 0.2-0.8，纯合子的 RR 为 0.6，95%CI = 0.2-1.5)。母体 AGT 单倍型 t-c-g 和 C-c-g 纯合子似乎有更高的风险，但只有前者具有统计学意义。我们仅发现胎儿 REN 单倍型的总体效应的微弱证据，并且没有证据支持我们的假设，即 REN 的效应取决于母亲是否携带 AGT 的 C-T-A 单倍型 (p = 0.33)。
我们的研究结果表明，母体的 AGT 单倍型影响其发生子痫前期的风险。然而，这种风险不受胎儿 REN 单倍型的影响。
