Morgan L, Crawshaw S, Baker P N, Broughton Pipkin F, Kalsheker N
Department of Clinical Laboratory Sciences, University Hospital, Nottingham, UK.
Br J Obstet Gynaecol. 1999 Mar;106(3):244-51. doi: 10.1111/j.1471-0528.1999.tb08238.x.
To compare the angiotensinogen genotypes in normotensive and pre-eclamptic pregnancies in maternal and fetal samples.
Prospective observational study.
University Hospital, Queen's Medical Centre, Nottingham.
Forty-three women with pre-eclampsia and 84 normotensive pregnant women. Fetal samples were available for genotyping from 96% of the pregnancies.
Maternal and fetal DNA was genotyped at angiotensinogen codon 235 and at a dinucleotide repeat polymorphism in the 3' flanking region of the gene. Angiotensinogen and renin concentrations were measured in maternal plasma by radioimmunoassay.
In contrast to earlier studies, no association was demonstrated between the angiotensinogen 235 Thr variant and pre-eclampsia. Normotensive pregnant women homozygous for this variant had significantly lower plasma angiotensinogen concentrations (median 2.2 ng AI/mL; IQR 1.8-3.0) than women homozygous for the 235 Met allele (3.6 ng AI/mL; IQR 2.5-4.1; P = 0.04). In pre-eclamptic pregnancies, 79% (11/14) of mothers heterozygous for the dinucleotide repeat allele designated A9 transmitted this allele to the fetus, more frequently than would be expected by chance (P = 0.02). The A9 allele was associated with low plasma angiotensinogen concentrations (P = 0.001) and high renin concentrations (P = 0.02) in normotensive women.
There is no evidence that the angiotensinogen 235 Thr allele is associated with pre-eclampsia in the Nottingham population. The angiotensinogen 235 Thr allele is associated with low plasma angiotensinogen concentrations in normotensive pregnant women, in contrast to the high levels associated with this variant in non-pregnant women, suggesting that regulation of angiotensinogen expression in normal pregnancy may differ significantly from that in the non-pregnant state. There is preliminary evidence that maternal-fetal transmission of an angiotensinogen allele associated with low plasma angiotensinogen concentrations is associated with pre-eclampsia. Impaired generation of angiotensin II at the maternal-fetal interface may be a factor in the pathogenesis of pre-eclampsia.
比较正常血压孕妇与子痫前期孕妇母血和胎儿样本中的血管紧张素原基因型。
前瞻性观察研究。
诺丁汉女王医疗中心大学医院。
43例子痫前期妇女和84例血压正常的孕妇。96%的妊娠可获得用于基因分型的胎儿样本。
对母血和胎儿DNA进行血管紧张素原第235密码子及该基因3'侧翼区二核苷酸重复多态性的基因分型。采用放射免疫分析法测定母血中血管紧张素原和肾素浓度。
与早期研究不同，未发现血管紧张素原235苏氨酸变异体与子痫前期之间存在关联。该变异体纯合的血压正常孕妇血浆血管紧张素原浓度（中位数2.2 ng AI/mL；四分位间距1.8 - 3.0）显著低于235甲硫氨酸等位基因纯合的孕妇（3.6 ng AI/mL；四分位间距2.5 - 4.1；P = 0.04）。在子痫前期妊娠中，二核苷酸重复等位基因A9杂合的母亲中有79%（11/14）将该等位基因传给胎儿，其发生频率高于随机预期（P = 0.02）。在血压正常的妇女中，A9等位基因与低血浆血管紧张素原浓度（P = 0.001）和高肾素浓度（P = 0.02）相关。
在诺丁汉人群中，没有证据表明血管紧张素原235苏氨酸等位基因与子痫前期有关。与非孕妇中该变异体相关的高水平不同，血管紧张素原235苏氨酸等位基因与血压正常孕妇的低血浆血管紧张素原浓度相关，这表明正常妊娠中血管紧张素原表达的调节可能与非妊娠状态有显著差异。有初步证据表明，与低血浆血管紧张素原浓度相关的血管紧张素原等位基因的母婴传递与子痫前期有关。母胎界面处血管紧张素II生成受损可能是子痫前期发病机制中的一个因素。
