Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage
Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage
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DOI：
10.1016/j.humimm.2010.02.001
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发表时间：
2010-05-01
期刊：
影响因子：
2.7
通讯作者：
Christiansen, Ole B.
中科院分区：
文献类型：
--
作者：
Kolte, Astrid M.;Steffensen, Rudi;Christiansen, Ole B.
人类白细胞抗原(HL A)-G基因外显子8的3‘-非翻译区存在14个碱基对的长插入(INS)/长缺失(Del)多态性，可能影响该基因的转录。携带G14BP INS与低水平的可溶性人类白细胞抗原-G相关，并增加复发性流产(RM)的风险。由于人类白细胞抗原(HL A)区存在强连锁不平衡(LD)，目前尚未鉴定出人类白细胞抗原G区的主要致病基因。对29个有两个或更多兄弟姐妹患有不明原因的红斑狼疮的高加索人家系进行了HLA-A、-B、-DRB1和-G14BP基因多态性的研究。G14bpINS与HLA-A*01、-A*11、-A*31、-B*08和DRB1*03呈强阳性表达，而G14BP INS与HLA-A*02、-A*03和-A*24呈强阴性表达。单倍型遗传自母亲的单倍型在先证者中显著增加(p=0.05)。先证者与母亲对母体G14INS阳性单倍型的亲和性增加，提示与人类白细胞抗原G基因相邻的染色体片段的母胎亲和性是女性后代在以后的生殖生活中经历RM的一个危险因素。(C)2010年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版，版权所有。
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-A*01, -A*11, -A*31, -B*08, and DRB1*03, whereas strong negative LD was found between G14bp ins and HLA-A*02, -A*03, and -A*24. 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. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.