Hum. Reprod. Advance Access published online on February 24, 2006
Human Reproduction, doi:10.1093/humrep/del036
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1 Department of Human Genetics; Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. BACKGROUND: HLA-G is a non-classical HLA with important immunomodulatory roles in pregnancy. A polymorphism in the promoter region, -725G, was previously associated with sporadic miscarriage in women who were unselected with respect to reproductive history. In this study, the transcription levels of different HLA-G promoter haplotypes were examined to determine whether the miscarriage-associated -725G allele influences transcription. METHODS: Five naturally occurring promoter haplotypes and three variant haplotypes created by site-directed mutagenesis were sub-cloned into luciferase expression vectors and transfected into JEG-3 cells. Expression levels of these eight haplotypes were examined in cultured cells before and after treatment with inter-feron-
Received November 29, 2005
Revised January 6, 2006
Accepted January 19, 2006
Article
The miscarriage-associated HLA-G -725G allele influences transcription rates in JEG-3 cells
C. Ober 1 *,
C. Billstrand 2,
S. Kuldanek 2,
and
Z. Tan 2
2 Department of Human Genetics, The University of Chicago, Chicago, IL, USA
C. Ober, E-mail: c-ober{at}genetics.uchicago.edu
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Abstract
(IFN-
), cytosine-5-DNA methyltransferase (M. SssI) and 5-aza-2'-deoxycytidine. Differences in expression levels between haplotypes were determined by analysis of variance (ANOVA). RESULT: Promoter haplotypes with the miscarriage-associated -725G allele were expressed at significantly higher levels in all culture conditions compared with otherwise identical haplotypes that had a -725C or -725T allele. CONCLUSION: Variation in the HLA-G promoter region influences transcription rates. Contrary to expectations, increased expression of HLA-G may be disadvantageous in some pregnancies.![]()
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