HLA-G gene polymorphism in a Japanese population

Polymorphism of the HLA-G gene in a Japanese population was investigated employing polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis, PCR sequence-specific oligonucleotide (SSO) analysis, and DNA direct sequencing. Nucleotide sequence variations in exons 2, 3, and 4 of the HLA-G gene in 54 healthy Japanese individuals were examined. In addition, seven Japanese samples carrying common HLA haplotypes were analyzed. In total, nine single-base substitutions compared with the sequence of G*01011 were identified: one in intron 1 (nucleotide position 970), one in exon 2 (the third base of codon 57: G --> A), three in intron 2 (1264, 1276, and 1292), three in exon 3 (the third base of codon 93: C --> T, the third base of codon 107: A --> T, and the first base of codon 110: C --> A), and one in intron 3 (2334). The substitution at codon 110 was non-synonymous and led to an amino acid substitution from leucine to isoleucine. The other three nucleotide substitutions in exons were synonymous. Through analysis of combinations of the exon 2, 3, and 4 nucleotide sequences we identified four alleles, which we provisionally designated GJ1, GJ2, GJ3, and GJ4. The allele frequencies were estimated to be 0.33, 0.16, 0.45, and 0.06, respectively. Nucleotide sequences of GJ1, GJ2, and GJ4 were identical to G*01011, the clone 7.0E, and G*01013, respectively. GJ3 was a newly observed allele and was officially designated G*0104 by the WHO Nomenclature Committee in January 1996. Strong positive associations were observed between HLA-G alleles and HLA-A, -B, or -DRB1 alleles.