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Fucosyltransferase Gene Polymorphisms and Lewisb-Negative Status Are Frequent in Swedish Newborns, With Implications for Infectious Disease Susceptibility and Personalized Medicine.

Authors
  • King, Jovanka R1, 2
  • Varadé, Jezabel1
  • Hammarström, Lennart1
  • 1 Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. , (Sweden)
  • 2 Department of Immunopathology, SA Pathology, Women's and Children's Hospital Campus, and Robinson Research Institute and Discipline of Paediatrics, School of Medicine, University of Adelaide, North Adelaide, South Australia. , (Australia)
Type
Published Article
Journal
Journal of the Pediatric Infectious Diseases Society
Publisher
Oxford University Press
Publication Date
Dec 27, 2019
Volume
8
Issue
6
Pages
507–518
Identifiers
DOI: 10.1093/jpids/piy085
PMID: 30544260
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Single-nucleotide polymorphisms (SNPs) in the fucosyltransferase genes FUT2 and FUT3 have been associated with susceptibility to various infectious and inflammatory disorders. FUT variations influence the expression of human histo-blood group antigens (HBGAs) (H-type 1 and Lewis), which are highly expressed in the gut and play an important role in microbial attachment, metabolism, colonization, and shaping of the microbiome. In particular, FUT polymorphisms confer susceptibility to specific rotavirus and norovirus genotypes, which has important global health implications. We designed a genotyping method using a nested polymerase chain reaction approach to determine the frequency of SNPs in FUT2 and FUT3, thereby inferring the prevalence of Lewisb-positive, Lewisb-negative, secretor, and nonsecretor phenotypes in 520 Swedish newborns. There was an increased frequency of homozygotes for the minor allele for 1 SNP in FUT2 and 4 SNPs in FUT3. Overall, 37.3% of newborns were found to have Lewis b negative phenotypes (Le (a+b-) or Le (a-b-). Using our new, sensitive genotyping method, we were able to genetically define the Le (a-b-) individuals based on their secretor status and found that the frequency of Lewis b negative newborns in our cohort was 28%. Given the high frequency of fucosyltransferase polymorphisms observed in our newborn cohort and the implications for disease susceptibility, FUT genotyping might play a future role in personalized health care, including recommendations for disease screening, therapy, and vaccination. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: [email protected]

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