The HLA-G 14 bp allele frequency in different populations: A global meta-analysis

HLA-G gene encodes a non-classical molecule of major histocompatibility complex with important immunomodulatory properties, being expressed, primarily by cytotrophoblasts during pregnancy, or in pathological conditions (autoimmune diseases, cancer, transplants and viral infections). The insertion of 14 bp in HLA-G 3'UTR region has been related to reduced mRNA levels, consequently affecting the protein levels. Due to its importance for gene expression and in the context of several physiopathologic conditions, we assessed, by meta-analysis, the global distribution of the HLA-G 14 bp insertion allele frequency. We searched genetic association studies, published between 1997 and 2018, indexed in the PubMed, Science Direct and Google Scholar databases, using the descriptor: "HLA-G 14 bp". All studies that presented allele counts in the healthy controls were included. We analyzed 20,755 individuals from 112 different populations of Africa, Asia, American and Europe. The global allelic frequency of HLA-G 14 bp insertion was 0.42 (95%CI=0.41-0.44). When stratifying according to the continents, we observed the highest allelic frequency in the African continent (0.51) and the lowest in the European continent (0.41). Our meta-analysis demonstrates that HLA-G 14 bp insertion allele have a similar distribution around the world, indicating a possible action of balancing selection.