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A systematic study of single-nucleotide polymorphisms in the A4GALT gene suggests a molecular genetic basis for the P1/P2 blood groups

Authors

  • Yin-Ju Lai,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Wan-Yi Wu,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Chen-Ming Yang,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Li-Rong Yang,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Chen-Chung Chu,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Yung-Syu Chan,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Marie Lin,

    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
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  • Lung-Chih Yu

    Corresponding author
    1. Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan
    2. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
    3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    4. Blood Bank, Mackay Memorial Hospital, Taipei, Taiwan
    • Address reprint requests to: Lung-Chih Yu, Institute of Biochemical Sciences, College of Life Science, National Taiwan University, No. 1, Roosevelt Road Section 4, Taipei 106, Taiwan; e-mail: yulc@ntu.edu.tw.

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  • This work was partially supported by Grants NSC 101-2311-B-014-MY3 and NSC 102-2321-B-002-057 from the National Science Council and Grant NTU-CESRP-103R76264A from the National Taiwan University, Taiwan.

Abstract

Background

The molecular mechanism for the formation of the P1/P2 blood groups remains unsolved. It has been shown that the P1/P2 polymorphism is connected to the different A4GALT gene expression levels in P1 and P2 red blood cells.

Study Design and Methods

The present investigation conducted a pilot investigation that involved the detailed and stepwise screening of single-nucleotide polymorphisms (SNPs) in the A4GALT gene, followed by a larger-scale association study. The transcription-inducing activity by the different genotypes of SNPs was analyzed using reporter assays.

Results

A total of 416 different SNP sites in the A4GALT genes from four P1 and four P2 individuals were analyzed in the pilot investigation, and 11 SNP sites, distributed in the A4GALT Intron 1 region, exhibited an association with the P1/P2 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 P1/P2 phenotypes. Reporter assays demonstrated significantly higher transcription-inducing activity by the SNPs bearing the P1-allele genotype than by the SNPs bearing the P2-allele genotype and that the difference in transcriptional activity was determined by the different genotypes at SNP rs5751348.

Conclusion

The results of this investigation demonstrate a consistent association of A4GALT SNPs rs2143918 and rs5751348 with the P1/P2 phenotypes and suggest that SNP rs5751348 may lead to allelic variations in A4GALT gene expression and consequently leads to the formation of the P1/P2 phenotypes.

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