SMIM1 intron 2 gene variations leading to variability in Vel antigen expression among Brazilian blood donors

• Published in: Blood cells, molecules, & diseases Vol. 77; pp. 23 - 28
• Main Authors: Dezan, Marcia Regina, Costa-Neto, Abel, Gomes, Carolina Nunes, Ribeiro, Ingrid Helena, Oliveira, Valéria Brito, Conrado, Marina C.A.V., Oliveira, Théo Gremen M., Carvalho, Mariana L.P., Aranha, Aline Fernanda, Bosi, Silvia R.A., Salles, Nanci A., Krieger, José Eduardo, Pereira, Alexandre Costa, Sabino, Ester Cerdeira, Rocha, Vanderson, Mendrone-Junior, Alfredo, Dinardo, Carla Luana, Levi, José Eduardo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019
• Subjects: Alleles; Antigenic Variation - genetics; Blood Donors; Brazil; Gene Expression Regulation; Gene Frequency; Genetic Association Studies; Genetic Variation; Genotype; Haplotypes; Humans; Introns; Linkage Disequilibrium; Membrane Proteins - genetics; Phenotype; Sequence Deletion; Brazil
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2019.03.006

There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.