relation between hla-g gene null allele (hla-g*0105n) and recurrent miscarriage

Human leukocyte antigen-g (hla-g) is a nonclassical hla-class i antigen located on chromosome 6. hla-g is highly expressed on cytotrophoblast cells at the fetomaternal interface and involved in the development of pregnant uterus as an immune privileged site. expression of hla-g is thought to have a critical role in the protection of the semiallogenic fetus from maternal immune attack during pregnancy. hla-g molecules bind inhibitory receptors on maternal t cells and nk cells and subsequently inhibit their cytolytic activities. because of mrna alternative splicing of hla-g primary transcript, the hla-g protein exists in both membrane-bound (hla-g1 to g4) and soluble (hla-g5 to g7) isoforms. hla-g gene contains 15 alleles, including the hla-g*0105n null allele. a single base-pair deletion of a cytosine (1597delc) results in open reading frame mutation, which leads to a premature stop codon. the hla-g*0105n allele is unable to generate the hla-g1, hla-g5, and hla-g4 isoforms. however, it is still able to produce other hla-g proteins, in which exon 3 is removed by alternative splicing, including hla-g2, g3, g6 and g7 isoforms. hla-g*0105n null allele has been described in healthy adults with successful and normal pregnancies, which suggests that hla-g function is not restricted to the hla-g1 isoform. description of healthy individual homozygous for hla-g*0105n allele recommends that truncated hla-g2 and g3 isoforms encoded by null allele are able to compensate for the lack of the hla-g1, g4 and g5 isoforms. results of the numerous studies on the null allele of hla-g gene indicated that its selection may have increased the frequency of the hla-g*0105n. studies on the null allele of hla-g gene could be useful in determining the frequency of genetic variants of hla-g alleles in different ethnic groups.