title: Genetic predisposition to parthenium dermatitis in an Indian cohort due to lower-producing genotypes of interleukin-10 (-) 1082 G>A and (-) 819 C>T loci but no association with interferon-γ (+) 874 A>T locus.
abstract: BACKGROUND
  Parthenium dermatitis is an activated T cell-mediated type IV hypersensitivity. Its pathogenesis is well characterized, with interindividually varying serum levels of pro- and anti-inflammatory and regulatory T-cell cytokines and coherently perturbed cross-regulation between them. The functional single nucleotide polymorphisms (SNPs) in these cytokine genes might function as risk/susceptibility factors for the disease.
  
  
  OBJECTIVE
  We analysed the serum levels of interferon (IFN)-γ and interleukin (IL)-10 cytokines in cases vs. controls and investigated whether IFN-γ (+) 874 A>T and IL-10 (-) 1082 G > A and (-) 819 C>T are associated with serum levels and genetically predispose to the disease.
  
  
  METHODS
  The study included 60 patch test-confirmed patients and 60 age- and sex-matched controls. The serum levels of cytokines were estimated by high-sensitivity enzyme-linked immunosorbent assay kits. SNP genotyping was performed by amplification refractory mutational system-polymerase chain reaction.
  
  
  RESULTS
  In patients, the serum level of IFN-γ was significantly increased and that of IL-10 was significantly decreased, with no difference in IgE concentration. Genetically no IFN-γ (+) 874 A>T alleles/genotypes were associated with the disease, but a strong predisposition was found due to lower-producing genotypes of IL-10 (-) 1082 G>A and (-) 819 C>T SNPs, with 2·1 and 3·5 times more risk, respectively, while intermediate IL-10-producing genotypes provided resistance.
  
  
  CONCLUSIONS
  High serum IFN-γ might play a role in disease pathogenesis, but this is genetically not endowed by the IFN-γ SNP studied. In contrast, low serum IL-10 was very much connected, with the genetics of both studied IL-10 loci. These might be key managing factors concerning pathogenesis/susceptibility.
authors.affiliation: School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
authors.forename: R
authors.initials: R
authors.lastname: Khatri
authors.forename: K
authors.initials: K
authors.lastname: Mukhopadhyay
authors.forename: K K
authors.initials: KK
authors.lastname: Verma
authors.forename: G
authors.initials: G
authors.lastname: Sethuraman
authors.forename: A
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000328:Adult; D019659:Asteraceae / Q000009:adverse effects; D015331:Cohort Studies; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007194:India; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics*; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D010328:Patch Tests
chemical_list: D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma