Hylenius Sine, Andersen Anne-Marie Nybo, Melbye Mads, Hviid Thomas Vauvert F
Department of Clinical Biochemistry, Copenhagen University Hospital, H:S Hvidovre Hospital, 30 Kettegaard Allé, DK-2650 Hvidovre, Denmark.
Mol Hum Reprod. 2004 Apr;10(4):237-46. doi: 10.1093/molehr/gah035. Epub 2004 Jan 29.
Pre-eclampsia affects 2-7% of all pregnancies with varying severity and is a leading cause of maternal and fetal mortality and morbidity. The aetiology involves almost certainly a combination of genetic predisposition with maternal and fetal contributions and environmental factors. Research points towards pathologies in the placenta as the triggering factor which leads to systemic endothelial dysfunction in the mother, probably as the result of interaction with released placental factors circulating in the maternal blood. One prominent hypothesis regarding the aetiology of pre-eclampsia suggests that it is caused by immune- maladaptation. The MHC class Ib gene, HLA-G, is expressed in the placenta and seems to have immunomodulatory functions. Aberrant HLA-G mRNA and protein expression in pre-eclamptic placentas have been reported. Here, we have investigated detailed HLA-G genotypes in a case-control study of 155 family triads of mother, father and newborn. Among primiparas, an overrepresentation of a homozygous HLA-G genotype was detected in the 40 pre-eclamptic offspring compared to the 70 controls [P = 0.002, Fisher's exact test; odds ratio 5.57 (95% CI 1.79-17.31)]. Further analyses suggested that the differences between pre-eclamptic cases and controls primarily were accomplished by a different transmission from the father of a 14 bp deletion/insertion polymorphism in exon 8 (P = 0.006, Fisher's exact test), which previously has been linked to differences in the levels of HLA-G expression and in HLA-G mRNA splicing. The results may also indicate that combined mother-child HLA-G genotypes could influence the risk of developing pre-eclampsia. Overall, the study suggests that HLA-G genotypes and expression might have a significant influence on development of pre-eclampsia.
子痫前期影响2%至7%的所有妊娠，严重程度各异，是孕产妇和胎儿死亡及发病的主要原因。其病因几乎肯定是遗传易感性与母婴因素及环境因素共同作用的结果。研究表明，胎盘病变是引发因素，可导致母亲全身内皮功能障碍，这可能是与母体血液中循环的胎盘释放因子相互作用的结果。关于子痫前期病因的一个重要假说是，它是由免疫适应不良引起的。MHC Ib类基因HLA - G在胎盘中表达，似乎具有免疫调节功能。已有报道称子痫前期胎盘存在异常的HLA - G mRNA和蛋白表达。在此，我们在一项针对155个母亲、父亲和新生儿家庭三联体的病例对照研究中，详细调查了HLA - G基因型。在初产妇中，与70名对照相比，40名子痫前期患儿中纯合HLA - G基因型的比例过高[P = 0.002，Fisher精确检验；优势比5.57(95%可信区间1.79 - 17.31)]。进一步分析表明，子痫前期病例与对照之间的差异主要是由父亲传递的外显子8中14 bp缺失/插入多态性的不同所致(P = 0.006，Fisher精确检验)，此前该多态性与HLA - G表达水平及HLA - G mRNA剪接差异有关。结果还可能表明，母婴HLA - G基因型组合可能影响子痫前期的发病风险。总体而言，该研究表明HLA - G基因型和表达可能对子痫前期的发生有显著影响。
