Genetic susceptibility to non-necrotizing erysipelas/cellulitis

PLoS One. 2013;8(2):e56225. doi: 10.1371/journal.pone.0056225. Epub 2013 Feb 20.

Abstract

Background: Bacterial non-necrotizing erysipelas and cellulitis are often recurring, diffusely spreading infections of the skin and subcutaneous tissues caused most commonly by streptococci. Host genetic factors influence infection susceptibility but no extensive studies on the genetic determinants of human erysipelas exist.

Methods: We performed genome-wide linkage with the 10,000 variant Human Mapping Array (HMA10K) array on 52 Finnish families with multiple erysipelas cases followed by microsatellite fine mapping of suggestive linkage peaks. A scan with the HMA250K array was subsequently performed with a subset of cases and controls.

Results: Significant linkage was found at 9q34 (nonparametric multipoint linkage score (NPL(all)) 3.84, p=0.026), which is syntenic to a quantitative trait locus for susceptibility to group A streptococci infections on chromosome 2 in mouse. Sequencing of candidate genes in the 9q34 region did not conclusively associate any to erysipelas/cellulitis susceptibility. Suggestive linkage (NPL(all)>3.0) was found at three loci: 3q22-24, 21q22, and 22q13. A subsequent denser genome scan with the HMA250K array supported the 3q22 locus, in which several SNPs in the promoter of AGTR1 (Angiotensin II receptor type I) suggestively associated with erysipelas/cellulitis susceptibility.

Conclusions: Specific host genetic factors may cause erysipelas/cellulitis susceptibility in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cellulitis / genetics*
  • Chromosomes, Human, Pair 9 / genetics
  • Erysipelas / genetics*
  • Family
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics
  • Genotyping Techniques
  • Humans
  • Male
  • Mice
  • Microsatellite Repeats / genetics
  • Oligonucleotide Array Sequence Analysis
  • Pedigree
  • Physical Chromosome Mapping
  • Reproducibility of Results

Substances

  • Genetic Markers

Grants and funding

This work was supported by the Academy of Finland/Microbes and Man Research Program, Helsinki Biomedical Graduate School, Sigrid Jusélius Foundation, and the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.