Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads
Association between HLA-G genotype and risk of pre-eclampsia: a case-control study using family triads
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DOI：
10.1093/molehr/gah035
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发表时间：
2004-04-01
影响因子：
4
通讯作者：
Hviid, TVF
中科院分区：
文献类型：
--
作者：
Hylenius, S;Andersen, AMN;Hviid, TVF
子痫前期影响2 - 7%的妊娠，严重程度不一，是孕产妇和胎儿死亡及发病的主要原因。其病因几乎肯定涉及遗传易感性以及母体和胎儿因素与环境因素的综合作用。研究表明胎盘的病理改变是触发因素，它导致母体全身性内皮功能障碍，这可能是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认为它是由免疫适应不良引起的。主要组织相容性复合体（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的HLA - G mRNA和蛋白质表达异常。在此，我们在一项对155个母亲、父亲和新生儿的家庭三联体进行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例对照相比，在40例子痫前期后代中检测到纯合HLA - G基因型的比例过高[P = 0.002，费舍尔精确检验；比值比5.57（95%置信区间1.79 - 17.31）]。进一步分析表明，子痫前期病例和对照之间的差异主要是由父亲传递外显子8中14bp缺失/插入多态性的差异造成的（P = 0.006，费舍尔精确检验），此前该多态性已与HLA - G表达水平和HLA - G mRNA剪接的差异有关。研究结果还可能表明，母子HLA - G联合基因型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展有重大影响。
Pre-eclampsia affects 2-7% of all pregnancies with varying severity and is a leading cause of maternal and fetal mortality and morbidity. The aetihology 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.