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Reproductive Sciences
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Association Between Novel HLA-G Genotypes and Risk of Recurrent Miscarriages: A Case-Control Study in a South Indian Population

Venkata Suryanarayana, MSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Lakshmi Rao, MSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Murthy Kanakavalli, MSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Venkata Padmalatha, MSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Turalpati Raseswari, MSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Mamata Deenadayal, MD

Infertility Institute and Research Centre, Secunderabad, Andhra Pradesh, India

Lalji Singh, DSc

Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India, lalji{at}ccmb.res.in

HLA-G is a nonclassical histocompatibility complex member associated with fetal tolerance of the mother observed during pregnancy. Despite its being a less polymorphic gene, a number of studies have evaluated the role of HLA-G gene polymorphisms on the risk of pregnancy-related complications. A 14-bp deletion polymorphism in exon 8 (3'UTR) was known to influence the levels of soluble HLA-G, differential splicing of the transcript, and also the induction of interleukin-10 secretion. The present study is aimed at evaluating the variations in exon 2 and exon 8 of the HLA-G gene for the risk of recurrent miscarriages in South Indian women. A total of 169 cases and 92 controls are included in the study. Six novel polymorphisms were identified, 2 of which are in intron 2 near the exon-intron junction and 4 of which are present downstream to the 14-bp deletion in 3'UTR. The exon 2 and intron polymorphisms failed to show any association. The T1570C and C1594A polymorphisms showed a significant association (P = .002 and .021) with the risk of miscarriage after categorization based on the 14-bp deletion. Linkage disequilibrium analysis showed that the T allele of T1570C is in linkage disequilibrium with the 14-bp deletion in cases but not in controls. In silico RNA folding studies indicate that the T allele forms a more stable secondary structure than the C allele, giving rise to a more stable transcript.The authors demonstrate a significant relation between the two 3'UTR polymorphisms and recurrent miscarriages.

Key Words: Recurrent miscarriages • HLA-G ;polymorphisms • association.

This version was published on October 1, 2008

Reproductive Sciences, Vol. 15, No. 8, 817-824 (2008)
DOI: 10.1177/1933719107314061
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