title: Detection and functional evaluation of -262A/T and -188A/G polymorphisms of SLAM gene in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the -262A/T and -188A/G polymorphisms of SLAM in Chinese patients with SLE.
  
  
  METHODS
  Genotyping of -262A/T (rs2295614) and -188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction.
  
  
  RESULTS
  Frequencies of -262A allele and -188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152-1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in -262A-188G haplotype homozygotes compared with -262A-188G heterozygotes and individuals with other genotypes.
  
  
  CONCLUSIONS
  Our findings suggest that -262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Shapingba District, Chongqing, 400038, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: You
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Deng
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
mesh_terms: D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1