Morgan L, Crawshaw S, Baker P N, Brookfield J F, Broughton Pipkin F, Kalsheker N
Department of Clinical Laboratory Sciences, University Hospital, Queen's Medical Centre, Nottingham, UK.
J Med Genet. 1998 Aug;35(8):632-6. doi: 10.1136/jmg.35.8.632.
To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia.
Case-control study.
Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies.
Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region.
Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission.
Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion.
研究子痫前期胎儿血管紧张素II 1型受体基因型。
病例对照研究。
41对来自子痫前期妊娠的母婴对和80对来自血压正常妊娠的母婴对。
对血管紧张素II 1型受体基因编码外显子中核苷酸573、1062和1166处的三个双等位基因多态性以及其3'侧翼区域的一个二核苷酸重复多态性进行母婴DNA基因分型。
在所研究的四个多态性区域，子痫前期组和血压正常组的胎儿或母亲样本中的等位基因和基因型频率均无差异。二核苷酸重复等位基因命名为A4的杂合母亲，在18例有信息的子痫前期妊娠中有15例将该等位基因传递给胎儿，在26例血压正常妊娠中有8例传递给胎儿。这高于子痫前期妊娠中的预期概率（p = 0.04），低于血压正常妊娠中的预期概率（p < 0.005）。与A4等位基因存在部分连锁不平衡的573T变体，在母婴传递中表现出类似的偏差。
胎儿血管紧张素II 1型受体基因表达可能与子痫前期的病因有关。尚不清楚易感性是由胎儿基因型单独作用导致，还是由母亲和胎儿的等位基因共享导致。573T变体与血小板表面受体低表达水平相关，提示了血管紧张素II 1型受体基因作用的可能机制。如果胎盘受体表达同样由基因决定，对血管紧张素II的反应性可能会受到影响，从而有可能影响胎盘形成或胎盘前列腺素分泌。
