Christiansen O B, Andersen H H, Højbjerre M, Kruse T A, Lauritzen S L, Grunnet N
Department of Obstetrics and Gynaecology, Aalborg University, Denmark.
Eur J Immunogenet. 1995 Aug;22(4):323-34. doi: 10.1111/j.1744-313x.1995.tb00248.x.
The HLA allogenotypes DR1/Br, DR3 and DR10 (entitled risk HLA markers) have been reported as being genetic markers for the predisposition to experience unexplained recurrent fetal losses. The aim of the study was to determine whether the putative risk HLA markers might also be markers for the risk of pregnancy loss in sisters and wives of brothers of women with unexplained recurrent fetal losses. Information concerning pregnancy outcomes among the relatives of 146 consecutive women with unexplained recurrent fetal losses was collected. Ninety-five of the full sisters, 69 of the full brothers and 50 of the wives of the brothers were HLA typed. Sisters who had experienced at least one previous pregnancy loss (affected women) shared more HLA haplotypes with the proband than unaffected sisters, when the proband was positive for the risk markers (P = 0.02). More affected than unaffected sisters and brothers' wives were positive for the risk markers (P < 0.005 and P < 0.03; respectively). The lowest estimate of the odds ratio for experiencing pregnancy loss among sisters and brothers' wives who were positive compared with those negative for the risk markers was 3.5 (95% credible interval = 1.9-5.8). It is concluded that maternal DR1/Br, DR3 and DR10 allogenotypes seem to be genetic markers for the risk of pregnancy loss among relatives of women with unexplained recurrent fetal losses. The pattern of inheritance suggests a polygenic mode of inheritance with alleles linked to the risk HLA markers interacting with non-HLA linked genes expressed on the fetus or the trophoblast.
人类白细胞抗原（HLA）同种基因型DR1/Br、DR3和DR10（被称为风险HLA标记）已被报道为不明原因复发性流产易感性的遗传标记。本研究的目的是确定这些假定的风险HLA标记是否也可能是不明原因复发性流产女性的姐妹和兄弟之妻流产风险的标记。收集了146例连续的不明原因复发性流产女性亲属的妊娠结局信息。对95名亲姐妹、69名亲兄弟和50名兄弟之妻进行了HLA分型。当先证者的风险标记呈阳性时，至少经历过一次既往流产的姐妹（受影响女性）与先证者共享的HLA单倍型比未受影响的姐妹更多（P = 0.02）。风险标记呈阳性的受影响姐妹和兄弟之妻比未受影响的更多（分别为P < 0.005和P < 0.03）。与风险标记呈阴性的姐妹和兄弟之妻相比，呈阳性的姐妹和兄弟之妻流产的最低优势比估计值为3.5（95%可信区间 = 1.9 - 5.8）。得出的结论是，母体DR1/Br、DR3和DR10同种基因型似乎是不明原因复发性流产女性亲属流产风险的遗传标记。遗传模式表明是一种多基因遗传模式，与风险HLA标记相关的等位基因与在胎儿或滋养层上表达的非HLA连锁基因相互作用。
