title: Analysis of the association of HLA-DRB1, TNFalpha promoter and TNFR2 (TNFRSF1B) polymorphisms with SLE using transmission disequilibrium test.
abstract: A number of studies reported associations of HLA-DRB1, TNFalpha (TNF) promoter and TNF receptor II (TNFR2, TNFRSF1B) polymorphisms with systemic lupus erythematosus (SLE), however, the results have often been inconsistent. Such lack of consistency could partly derive from the population admixture involved in the case-control study. To avoid such a problem, polymorphisms in these genes were analyzed using transmission disequilibrium test (TDT) in Caucasian SLE families. Ninety-one Caucasian SLE family samples recruited in southern California were analyzed for the association with HLA-DRB1, TNF promoter positions at -1031, -863, -857 and -308, and TNFR2-196M/R polymorphisms. Significant transmission was observed for HLA-DRB1*1501, but not for HLA-DRB1*0301, nor for TNF haplotype that codes for -308A. Interestingly, TNF haplotype coding for -1031C, -863A, -857C showed a tendency of preferential nontransmission in the patients without lupus nephritis and in those with malar rash. No transmission distortion was observed for TNFR2-196R allele. These findings confirmed the association of HLA-DRB1*1501, but did not replicate that of the HLA-DRB1*0301, TNFA-308A and TNFR2-196R with SLE in this population. In addition, a possible disease-protective role for TNF haplotype coding for -1031C, -863A, -857C was suggested.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. tsuchiya-tky@umin.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: A
authors.initials: A
authors.lastname: Kawasaki
authors.forename: B P
authors.initials: BP
authors.lastname: Tsao
authors.forename: T
authors.initials: T
authors.lastname: Komata
authors.forename: J M
authors.initials: JM
authors.lastname: Grossman
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D009679:Nuclear Family; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha