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Mol. Hum. Reprod. Advance Access published online on October 24, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan059
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A single base-pair mutation in the 3’-untranslated region of HLA-G mRNA is associated with preeclampsia

Shang-mian Yie1,2, Liang-hong Li1, Rong Xiao1 and Clifford L. Librach1,3

1Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre and Women's College Hospital, University of Toronto, Toronto, Ontario, Canada, M5G 1N8 2Core Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Chengdu, Sichuan, P.R. China, 610072

3 Corresponding Author and Reprint Requests: Clifford L. Librach, M.D., 790 Bay Street, Suite 1100, Toronto, Ontario, Canada, M5G 1N8, Phone: (416) 323-7727, Fax: (416) 323-7334, E-mail: cliffl{at}ican.net

Human leukocyte antigen-G (HLA-G) is a non-classical class I HLA molecule that is expressed by extravillous cytotrophoblast cells. This protein may play a critical role in the protection of cytotrophoblasts from maternal immune response, allowing these semi-allogeneic cells to invade the uterus unimpeded. We have demonstrated that diminished placental HLA-G expression is associated with preeclampsia. In order to explore fundamental mechanisms underlying this reduced HLA-G expression in preeclampsia, we looked for, and found by sequences analysis, a single base-pair mutation in the HLA-G gene 3’-untranslated region (3’UTR) adjacent to an AUUUA motif. This mutation is significantly associated with preeclampsia, the severe form being more strongly associated with homozygosity for this mutation than the mild form. Since the null allele was discovered in the HLA-G mRNA 3’UTR adjacent to an AUUUA motif, we also examined the effect of this mutation on HLA-G mRNA stability, and found that half-lives of HLA-G mRNA with the mutation were significantly shorter than without the mutation. These data provide evidence that this mutation could be one of the fundamental mechanisms for lower levels of placental HLA-G protein expression in patients with preeclampsia.

Key Words: HLA-G/gene mutation/RNA stability/preeclampsia

Submitted on May 5, 2008; resubmitted on September 22, 2008; accepted on September 24, 2008.


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