Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Hum Immunol. 2010 May;71(5):482-8. doi: 10.1016/j.humimm.2010.02.001. Epub 2010 Feb 19.
A 14-base pair (bp) long insertion (ins)/deletion (del) polymorphism in exon 8 in the 3'-untranslated region of the human leukocyte antigen (HLA)-G gene is suggested to affect transcription of the gene. Carriage of the G14bp ins is associated with low levels of soluble HLA-G and increases the risk of recurrent miscarriage (RM). Due to existence of strong linkage disequilibrium (LD) in the HLA region, the primary susceptibility genes for RM in the HLA-G region have not yet been identified. HLA-A, -B, -DRB1, and -G14bp polymorphisms were investigated in 29 Caucasian families with two or more siblings suffering unexplained RM. Strong positive LD was detected between the G14bp ins and HLA-A01, -A11, -A31, -B08, and DRB103, whereas strong negative LD was found between G14bp ins and HLA-A02, -A03, and -A24. The frequency of haplotypes with HLA-G14bp ins inherited from the mother was significantly increased in probands with RM (p = 0.05). The increased compatibility between probands and their mothers for maternal G14 ins positive haplotypes suggests that maternal-fetal compatibility for chromosomal segments adjacent to HLA-G locus is a risk factor for female offspring to experience RM in their later reproductive life.
在人类白细胞抗原（HLA）-G 基因的 3'-非翻译区的外显子 8 中存在 14 个碱基对（bp）的插入（ins）/缺失（del）多态性，提示其可能影响基因转录。携带 G14bpins 的个体可溶性 HLA-G 水平较低，增加了复发性流产（RM）的风险。由于 HLA 区域存在强烈的连锁不平衡（LD），HLA-G 区域中 RM 的主要易感基因尚未确定。在 29 个具有两个或更多不明原因 RM 同胞的高加索家族中，研究了 HLA-A、-B、-DRB1 和-G14bp 多态性。在 G14bp ins 与 HLA-A01、-A11、-A31、-B08 和 DRB103 之间检测到强烈的正 LD，而在 G14bp ins 与 HLA-A02、-A03 和 -A24 之间检测到强烈的负 LD。从母亲那里遗传的 HLA-G14bp ins 单倍型的频率在 RM 患者中显著增加（p = 0.05）。RM 患者与其母亲之间存在与母性 G14 插入阳性单倍型的高相容性表明，与 HLA-G 基因座相邻的染色体片段的母胎相容性是女性后代在其生殖后期经历 RM 的危险因素。
