MHC class II, tumour necrosis factor α, and lymphotoxin α gene haplotype associations with serological subsets of systemic lupus erythematosus

Abstract
Objective: To conduct a case–control study to investigate whether there are independent tumour necrosis factor α (TNFα) or lymphotoxin α (LTα) haplotype associations with SLE or with any of the major serological subsets of SLE. Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFα, and LTα alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFα, six single nucleotide polymorphisms (SNPs) at positions −1031, −863, −857, −308, −238, and +488 and for LTα three SNPs at positions +720, +365, and +249 were studied to assign six TNFα haplotypes (TNF1-6) and four LTα haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples. Results: The most significant association with SLE overall was with HLA-DR3 (pConclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFα alleles on an extended DR3 haplotype.

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