HLA-G exhibits low level of polymorphism in indigenous East Africans.
Human leukocyte antigen G (HLA-G) is a nonclassical HLA class I antigen that is predominantly expressed on invasive cytotrophoblastic cells, and is postulated to be a mediator of maternal-fetal tolerance. Almost all studies in Caucasian and Asian populations have consistently reported that HLA-G exhibits low levels of allelic polymorphism unlike the classical class I genes. However, the concept that HLA-G is nonpolymorphic has recently been challenged in a single study of African-American subjects. We have examined the DNA sequences of the first seven HLA-G exons by single-strand conformational polymorphism (SSCP) and DNA direct sequencing procedures in 45 healthy individuals from an indigenous African population. Overall, we detected 14 sequence variations: 3 in the signal peptide (exon 1); 2 in the alpha-1 domain (exon 2); 5 in the alpha-2 domain (exon 3); 2 in alpha-3 domain (exon 4); 2 in transmembrane domain (exon 5); and none in the cytoplasmic tail (exons 6 and 7). Of these variants, only three result in amino acid substitutions at the protein level. Of particular interest, we identified a novel nucleotide substitution (C727T), 56 bp before the HLA-G gene transcription start site, located in the putative binding site for polyomavirus enhancer-binding protein 2 (PEBP2) transcriptor factor. These data confirm previous reports describing HLA-G exhibiting limited allelic polymorphism. Further studies are needed to determine the impact of the C727T polymorphism on the level or developmental regulation of HLA-G expression.
Matte
Claudine
C
Laboratoire d'Immunogénétique, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Canada.
Lacaille
Julie
J
Zijenah
Lynn
L
Ward
Brian
B
Roger
Michel
M
D000351:Africa, Eastern; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D005091:Exons; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D001741:Black or African American
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I