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Hum Reprod. 2006 Jul;21(7):1743-8. Epub 2006 Feb 24.

The miscarriage-associated HLA-G -725G allele influences transcription rates in JEG-3 cells.

Author information

1
Department of Human Genetics, The University of Chicago, IL 60637, USA. c-ober@genetics.uchicago.edu

Abstract

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 interferon-beta (IFN-beta), 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.

PMID:
16501035
DOI:
10.1093/humrep/del036
[Indexed for MEDLINE]

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