A systematic study of single‐nucleotide polymorphisms in the A4GALT gene suggests a molecular genetic basis for the P1/P2 blood groups. Issue 12 (20th July 2014)

• Record Type: Journal Article
• Authors: Lai, Yin‐Ju; Wu, Wan‐Yi; Yang, Chen‐Ming; Yang, Li‐Rong; Chu, Chen‐Chung; Chan, Yung‐Syu; Lin, Marie; Yu, Lung‐Chih
• Is Part Of: Transfusion. Volume 54:Issue 12(2014)
• Page Start: 3222
• Page End: 3231
• Publication Date: 2014-07-20
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.12771
• Languages: English
• ISSNs: 0041-1132

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="trf12771-sec-0001" sec-type="section"> <title>Background</title> <p>The molecular mechanism for the formation of the P<sub>1</sub>/P<sub>2</sub> blood groups remains unsolved. It has been shown that the P<sub>1</sub>/P<sub>2</sub> polymorphism is connected to the different <italic>A4GALT</italic> gene expression levels in P<sub>1</sub> and P<sub>2</sub> red blood cells.</p> </sec> <sec id="trf12771-sec-0002" sec-type="section"> <title>Study Design and Methods</title> <p>The present investigation conducted a pilot investigation that involved the detailed and stepwise screening of single‐nucleotide polymorphisms (SNPs) in the <italic>A4GALT</italic> gene, followed by a larger‐scale association study. The transcription‐inducing activity by the different genotypes of SNPs was analyzed using reporter assays.</p> </sec> <sec id="trf12771-sec-0003" sec-type="section"> <title>Results</title> <p>A total of 416 different SNP sites in the <italic>A4GALT</italic> genes from four P<sub>1</sub> and four P<sub>2</sub> individuals were analyzed in the pilot investigation, and 11 SNP sites, distributed in the <italic>A4GALT</italic> Intron 1 region, exhibited an association with the P<sub>1</sub>/P<sub>2</sub> phenotypes. In the follow‐up association study, the genotypes at the 11 SNPs of a total of 338 individuals across four different ethnic populations were determined, and the results show that two SNPs, rs2143918 and rs5751348, are consistently associated with the P<sub>1</sub>/P<sub>2</sub> phenotypes. Reporter assays demonstrated significantly higher transcription‐inducing activity by the SNPs bearing the <italic>P<sup>1</sup></italic>‐allele genotype than by the SNPs bearing the <italic>P<sup>2</sup></italic>‐allele genotype and that the difference in transcriptional activity was determined by the different genotypes at SNP rs5751348.</p> </sec> <sec id="trf12771-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The results of this investigation demonstrate a consistent association of <italic>A4GALT</italic> SNPs rs2143918 and rs5751348 with the P<sub>1</sub>/P<sub>2</sub> phenotypes and suggest that SNP rs5751348 may lead to allelic variations in <italic>A4GALT</italic> gene expression and consequently leads to the formation of the P<sub>1</sub>/P<sub>2</sub> phenotypes.</p> </sec> </abstract>