Association between novel HLA-G genotypes and risk of recurrent miscarriages: a case-control study in a South Indian population.
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.
Suryanarayana
Venkata
V
Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India.
Rao
Lakshmi
L
Kanakavalli
Murthy
M
Padmalatha
Venkata
V
Raseswari
Turalpati
T
Deenadayal
Mamata
M
Singh
Lalji
L
D000026:Abortion, Habitual / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D004247:DNA