PMID- 26450422
OWN - NLM
STAT- MEDLINE
DCOM- 20160712
LR  - 20231111
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Print)
IS  - 0022-1899 (Linking)
VI  - 213
IP  - 5
DP  - 2016 Mar 1
TI  - Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to 
      Staphylococcus aureus Infection in a White Population.
PG  - 816-23
LID - 10.1093/infdis/jiv483 [doi]
AB  - 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 x 10(-10)]; rs35079132: OR, 1.24 [P = 
      3.8 x 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 x 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.
CI  - (c) The Author 2015. Published by Oxford University Press for the Infectious 
      Diseases Society of America. All rights reserved. For permissions, e-mail 
      journals.permissions@oup.com.
FAU - DeLorenze, Gerald N
AU  - DeLorenze GN
AD  - Division of Research, Kaiser Permanente Northern California, Oakland.
FAU - Nelson, Charlotte L
AU  - Nelson CL
AD  - Duke Clinical Research Institute.
FAU - Scott, William K
AU  - Scott WK
AD  - John P. Hussman Institute for Human Genomics Dr. John T. Macdonald Foundation 
      Department of Human Genetics, University of Miami Miller School of Medicine, 
      Florida.
FAU - Allen, Andrew S
AU  - Allen AS
AD  - Department of Biostatistics and Bioinformatics, Duke University School of 
      Medicine, Durham, North Carolina.
FAU - Ray, G Thomas
AU  - Ray GT
AD  - Division of Research, Kaiser Permanente Northern California, Oakland.
FAU - Tsai, Ai-Lin
AU  - Tsai AL
AD  - Division of Research, Kaiser Permanente Northern California, Oakland.
FAU - Quesenberry, Charles P Jr
AU  - Quesenberry CP Jr
AD  - Division of Research, Kaiser Permanente Northern California, Oakland.
FAU - Fowler, Vance G Jr
AU  - Fowler VG Jr
AD  - Duke Clinical Research Institute Division of Infectious Diseases, Duke University 
      Medical Center.
LA  - eng
GR  - R01 AI068804/AI/NIAID NIH HHS/United States
GR  - UL1 TR001117/TR/NCATS NIH HHS/United States
GR  - 2R01-AI068804/AI/NIAID NIH HHS/United States
GR  - UL1TR001117/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151008
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Histocompatibility Antigens Class II/genetics/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - *Polymorphism, Genetic
MH  - Staphylococcal Infections/*genetics/microbiology
MH  - Staphylococcus aureus/*physiology
MH  - White People/*genetics
MH  - Young Adult
PMC - PMC4747615
OTO - NOTNLM
OT  - HLA
OT  - Staphylococcus aureus
OT  - host genetics
EDAT- 2015/10/10 06:00
MHDA- 2016/07/13 06:00
PMCR- 2017/03/01
CRDT- 2015/10/10 06:00
PHST- 2015/07/21 00:00 [received]
PHST- 2015/09/30 00:00 [accepted]
PHST- 2017/03/01 00:00 [pmc-release]
PHST- 2015/10/10 06:00 [entrez]
PHST- 2015/10/10 06:00 [pubmed]
PHST- 2016/07/13 06:00 [medline]
AID - jiv483 [pii]
AID - 10.1093/infdis/jiv483 [doi]
PST - ppublish
SO  - J Infect Dis. 2016 Mar 1;213(5):816-23. doi: 10.1093/infdis/jiv483. Epub 2015 Oct 
      8.