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Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population.

Publication ,  Journal Article
DeLorenze, GN; Nelson, CL; Scott, WK; Allen, AS; Ray, GT; Tsai, A-L; Quesenberry, CP; Fowler, VG
Published in: J Infect Dis
March 1, 2016

BACKGROUND: Staphylococcus aureus can cause life-threatening infections. Human susceptibility to S. aureus infection may be influenced by host genetic variation. METHODS: A genome-wide association study (GWAS) in a large health plan-based cohort included biologic specimens from 4701 culture-confirmed S. aureus cases and 45 344 matched controls; 584 535 single-nucleotide polymorphisms (SNPs) were genotyped on an array specific to individuals of European ancestry. Coverage was increased by imputation of >25 million common SNPs, using the 1000 Genomes Reference panel. In addition, human leukocyte antigen (HLA) serotypes were also imputed. RESULTS: Logistic regression analysis, performed under the assumption of an additive genetic model, revealed several imputed SNPs (eg, rs115231074: odds ratio [OR], 1.22 [P = 1.3 × 10(-10)]; rs35079132: OR, 1.24 [P = 3.8 × 10(-8)]) achieving genome-wide significance on chromosome 6 in the HLA class II region. One adjacent genotyped SNP was nearly genome-wide significant (rs4321864: OR, 1.13; P = 8.8 × 10(-8)). These polymorphisms are located near the genes encoding HLA-DRA and HLA-DRB1. Results of further logistic regression analysis, in which the most significant GWAS SNPs were conditioned on HLA-DRB1*04 serotype, showed additional support for the strength of association between HLA class II genetic variants and S. aureus infection. CONCLUSIONS: Our study results are the first reported evidence of human genetic susceptibility to S. aureus infection.

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Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

March 1, 2016

Volume

213

Issue

5

Start / End Page

816 / 823

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Staphylococcus aureus
  • Staphylococcal Infections
  • Polymorphism, Genetic
  • Odds Ratio
  • Middle Aged
  • Microbiology
  • Male
  • Humans
 

Citation

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Chicago
ICMJE
MLA
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DeLorenze, G. N., Nelson, C. L., Scott, W. K., Allen, A. S., Ray, G. T., Tsai, A.-L., … Fowler, V. G. (2016). Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population. J Infect Dis, 213(5), 816–823. https://doi.org/10.1093/infdis/jiv483
DeLorenze, Gerald N., Charlotte L. Nelson, William K. Scott, Andrew S. Allen, G Thomas Ray, Ai-Lin Tsai, Charles P. Quesenberry, and Vance G. Fowler. “Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population.J Infect Dis 213, no. 5 (March 1, 2016): 816–23. https://doi.org/10.1093/infdis/jiv483.
DeLorenze GN, Nelson CL, Scott WK, Allen AS, Ray GT, Tsai A-L, et al. Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population. J Infect Dis. 2016 Mar 1;213(5):816–23.
DeLorenze, Gerald N., et al. “Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population.J Infect Dis, vol. 213, no. 5, Mar. 2016, pp. 816–23. Pubmed, doi:10.1093/infdis/jiv483.
DeLorenze GN, Nelson CL, Scott WK, Allen AS, Ray GT, Tsai A-L, Quesenberry CP, Fowler VG. Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population. J Infect Dis. 2016 Mar 1;213(5):816–823.
Journal cover image

Published In

J Infect Dis

DOI

EISSN

1537-6613

Publication Date

March 1, 2016

Volume

213

Issue

5

Start / End Page

816 / 823

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Staphylococcus aureus
  • Staphylococcal Infections
  • Polymorphism, Genetic
  • Odds Ratio
  • Middle Aged
  • Microbiology
  • Male
  • Humans