The+3010/C single nucleotide polymorphism (rs1710) at the HLA-G 3' untranslated region is associated with a short transcript exhibiting a deletion of 92 nucleotides

Author(s)

Castelli, Erick C. ; Paes, Gabriela Sato ; da Silva, Isabelle Mira ; Moreau, Philippe ; Donadi, Eduardo A.

• Document type: Journal article
• Source: IMMUNOGENETICS; v. 75, n. 2, p. 6-pg., 2023-03-07.

Abstract

The physiological expression of HLA-G is mainly observed in the placenta, playing an essential role in maternal-fetal tolerance. Among the HLA-G mRNA alternative transcripts, the one lacking 92 bases at the HLA-G 3 ' untranslated region (3 ' UTR), the 92bDel transcript, is more stable, is associated with increased HLA-G soluble levels, and was observed in individuals presenting a 14 bp insertion (14 bp(+)) at the 3 ' UTR. We investigated the presence of the 92bDel transcript in placenta samples, correlating its expression levels with the HLA-G polymorphisms at the 3 ' UTR. The 14 bp(+) allele correlates with the presence of the 92bDel transcript. However, the polymorphism triggering this alternative splicing is the + 3010/C allele (rs1710, allele C). Most 14 bp(+) haplotypes (UTR-2/-5/-7) present allele + 3010/C. However, 14 bp(- )haplotypes such as UTR-3 are also associated with + 3010/C, and the 92bDel transcript can be detected in homozygous samples for the 14 bp-allele carrying at least one copy of UTR-3. The UTR-3 haplotype is associated with alleles G*01:04 and the HLA-G lineage HG0104, which is a high-expressing lineage. The only HLA-G lineage that is not likely to produce this transcript is HG010101, associated with the + 3010/G allele. This functional difference may be advantageous, considering the high worldwide frequency of the HG010101 lineage. Therefore, HLA-G lineages are functionally distinct regarding the 92bDel transcript expression, and the 3010/C allele triggers the alternative splicing that produces this shorter and more stable transcript. (AU)

• FAPESP's process: 13/17084-2 - Evaluation of MHC Class I genes variability, regulation and evolutive history
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/14345-0 - 67th Annual Meeting of the American Society of Human Genetics
• Grantee: Erick da Cruz Castelli
• Support Opportunities: Research Grants - Meeting - Abroad