HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels
HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels
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DOI：
10.1007/s00251-003-0547-z
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发表时间：
2003-05-01
期刊：
影响因子：
3.2
通讯作者：
Nielsen, LG
中科院分区：
文献类型：
--
作者：
Hviid, TVF;Hylenius, S;Nielsen, LG
在怀孕期间，胎盘中母体和胎儿组织接触区的人绒毛外滋养细胞不表达经典的MHC I类和II类分子。相反，表达的是HLA-G和-C，可能还有HLA-E。HLA-G可能通过几种方式调节母体和胎儿之间的免疫关系。最后，膜结合HLA-G和可溶性HLA-G的表达已被提出影响妊娠结局，并且在子痫前期胎盘和自然流产中有异常HLA-G表达的报道。本文报道了妊娠早期滋养细胞群体中某些HLA-G多态性与不同的可选剪接HLA-G亚型mRNA水平之间的关联。一些可选择剪接的HLA-G mRNA异构体，包括HLA-G基因3'UTR端（外显子8）的14bp多态性，其表达水平明显低于相应的14bp序列缺失的HLA-G mRNA异构体。此外，HLA-G mRNA的特征亚型、表达模式与特定的HLA-G基因型和等位基因相关。在包含14bp序列的HLA-G*01012和-G*01013等位基因中，观察到额外的选择性剪接，第8外显子的前92bp被剪接掉。这在带有G*01013的HLA-G基因型中最为明显。这些发现可能对最近报道的异常HLA-G表达和生殖成功具有功能意义。
During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a significantly lower level than the corresponding HLA-G mRNA isoforms with the 14-bp sequence deleted. Furthermore, characteristic HLA-G mRNA isoform, expression patterns were associated with specific HLA-G genotypes and alleles. In the HLA-G*01012 and -G*01013 alleles that include the 14-bp sequence, an additional alternative splicing was observed, with the first 92-bp of exon 8 spliced out. This was most pronounced in HLA-G genotypes with G*01013. These findings may have functional implications for the recent reports of aberrant HLA-G expression and reproductive success.