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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • DeLorenze, GN; Nelson, CL; Scott, WK; Allen, AS; Ray, GT; Tsai, A-L; Quesenberry, CP; Fowler, VG

Published Date

  • March 1, 2016

Published In

Volume / Issue

  • 213 / 5

Start / End Page

  • 816 - 823

PubMed ID

  • 26450422

Pubmed Central ID

  • 26450422

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiv483

Language

  • eng

Conference Location

  • United States