High frequency of the HLA-G*01:05N null allele in Beninese populations and its potential impact on reduced soluble HLA-G expression

Abstract

Human Leucocyte Antigen (HLA)-G, a non-classical HLA class Ib molecule, is involved in feto-maternal immune tolerance. Among HLA-G alleles, HLA-G*01:05N is defined by a cytosine deletion (ΔC) at exon 3, which causes a premature stop codon at position 189 in exon 4, disrupting the translation of HLA-G1, HLA-G4, and HLA-G5 isoforms. The modulation of HLA-G expression in carriers of the HLA-G*01:05N allele could have important immune and pathologic consequences. We investigated the HLA-G*01:05N allele frequency in two Beninese populations and evaluated its association with HLA-G plasma levels. HLA-G*01:05N allele frequency was assessed by PCR/RFLP or by imputation from OMNI5 genotyping array data from 867 DNA samples collected in two cohorts in Southern Benin. Plasma sHLA-G concentration was measured by ELISA. HLA-G*01:05N allele frequency was 10.05% in the Tori Bossito cohort (n = 557) and 13.06% in the Allada cohort (n = 310), which representing the highest frequencies reported among African populations based on the 1000 Genomes project. Heterozygous individuals (CΔC) for HLA-G*01:05N had lower plasma sHLA-G levels compared to individuals without this allele. The number of individuals homozygous for HLA-G*01:05N with sHLA-G measurement was too low to confirm a difference in HLA-G levels compared with the other genotypes. The high frequency of the HLA-G*01:05N allele observed in Benin suggests that reduced sHLA-G expression in HLA-G*01:05N carriers may contribute to enhanced defense against infectious diseases.