title: CD8A gene polymorphisms predict severity factors in chronic rhinosinusitis.
abstract: BACKGROUND
  A genetic basis to chronic rhinosinusitis (CRS) is postulated, but remains elusive. We have recently identified low levels of circulating CD8 lymphocytes as a frequent finding in difficult-to-treat or refractory CRS. In major histocompatibility complex 1 class 1 (MHC1) deficiency, low circulating levels of CD8 lymphocytes secondary to mutations in the cluster of differentiation 8a (CD8A), tapasin 1 (TAP1), tapasin 2 (TAP2), or tapasin binding-protein (TAPBP) genes lead to a clinical syndrome, which is associated with severe CRS. The objective of this work was to identify whether genetic factors associated with MHC1 deficiency are present in CRS.
  
  
  METHODS
  Previous results from a genomewide association study of CRS were screened for polymorphisms in the CD8A, TAP1, TAP2, and TAPBP genes associated with MHC1 immunodeficiency syndrome. Significant polymorphisms were tested for associations with demographic factors characterizing severe CRS.
  
  
  RESULTS
  Polymorphisms in the CD8A (rs3810831) and TAPBP (rs2282851) genes were significantly associated with CRS. Major allele homozygosity for CD8A (rs3810831) was associated with a higher frequency of affected relatives (p = 0.052), increased severity as characterized by age at diagnosis (p = 0.009), age at first surgery (p = 0.004), and number of surgeries (p = 0.008), whereas TAPBP (rs2282851) was associated increased risk for CRS (odds ratio [OR] = 2.48, p = 0.0076).
  
  
  CONCLUSIONS
  Modified CD8A or TAPBP gene function may contribute to the development of refractory CRS via altered MHC1 function and reduction of circulating CD8 lymphocytes. Identification of markers in the CD8A or TAPBP genes via sequencing may offer a basis for genetic testing in CRS.
authors: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.
authors: Saud
authors: S
authors: Alromaih
authors: Leandra
authors: L
authors: Mfuna-Endam
authors: Yohan
authors: Y
authors: Bosse
authors: Abdelali
authors: A
authors: Filali-Mouhim
authors: Martin
authors: M
authors: Desrosiers
mesh_terms: D000328:Adult; D000368:Aged; D016827:CD8 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012220:Rhinitis / Q000235:genetics* / Q000378:metabolism; D012852:Sinusitis / Q000235:genetics* / Q000378:metabolism
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D026901:Membrane Transport Proteins; C107762:tapasin
keywords: CD8A; MHC1 deficiency; MHC1 immunodeficiency syndrome; TABP phenotyping; chronic rhinosinusitis; genetic association study