Impact of genetic variation in the SMIM1 gene on Vel expression levels

• Published in: Transfusion (Philadelphia, Pa.) Pa.), 2015-06, Vol.55 (6pt2), p.1457-1466
• Main Authors: Haer-Wigman, Lonneke, Stegmann, Tamara C., Solati, Shabnam, Ait Soussan, Aïcha, Beckers, Erik, van der Harst, Pim, van Hulst-Sundermeijer, Marga, Ligthart, Peter, van Rhenen, Dick, Schepers, Hein, de Haas, Masja, van der Schoot, C. Ellen
• Format: Article
• Language: English
• Subjects: Alleles; Blood Donors - statistics & numerical data; Blood Group Antigens - genetics; Continental Population Groups - genetics; Genetic Variation; Genotype; HEK293 Cells; Humans; Membrane Proteins - genetics; Phenotype; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Sequence Deletion; Transfection
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.13014

BACKGROUND Serologic determination of the Vel– phenotype is challenging due to variable Vel expression levels. In this study we investigated the genetic basis for weak Vel expression levels and developed a high‐throughput genotyping assay to detect Vel– donors. STUDY DESIGN AND METHODS In 548 random Caucasian and 107 Vel+w donors genetic variation in the SMIM1 gene was studied and correlated to Vel expression levels. A total of 3366 Caucasian, 621 black, and 333 Chinese donors were screened with a high‐throughput genotyping assay targeting the SMIM1*64_80del allele. RESULTS The Vel+w phenotype is in most cases caused by the presence of one SMIM1 allele carrying the major allele of the rs1175550 SNP in combination with a SMIM1*64_80del allele or in few cases caused by the presence of the SMIM1*152T>A or SMIM1*152T>G allele. In approximately 6% of Vel+w donors genetic factors in SMIM1 could not explain the weak expression. We excluded the possibility that lack of expression of another blood group system was correlated with weak Vel expression levels. Furthermore, using a high‐throughput Vel genotyping assay we detected two Caucasian Vel– donors. CONCLUSION Weak Vel expression levels are caused by multiple genetic factors in SMIM1 and probably also by other genetic or environmental factors. Due to the variation in Vel expression levels, serologic determination of the Vel– phenotype is difficult and a genotyping assay targeting the c.64_80del deletion in SMIM1 should be used to screen donors for the Vel– phenotype.