Relationship of tumour necrosis factor alpha gene polymorphisms and neuropsychiatric lupus

Systemic lupus erythematosus (SLE) is a multisystem disorder which appears to be influenced by genetic make-up. In this study we determine allele frequency and genotype distribution of TNFalpha polymorphisms in two populations of SLE patients (with and without neuropsychiatric manifestations) in order to determine whether the rare allele (TNF2) confers susceptibility for neuropsychiatric disease in SLE. Patients with SLE were retrospectively reviewed to determine presence (n = 17) or absence (n = 47) of documented neuropsychiatric manifestations attributable to SLE. The DNA from these patients was extracted from peripheral blood mononuclear cells, and PCR amplification, NcoI enzyme digestion and 10% polyacrylamide gel electrophoresis were performed to define the different TNFalpha alleles. Two alleles were demonstrated, TNF1 (wild-type) and TNF2 (rare type), with three possible genotypes, TNF1,1, TNF1,2 and TNF2,2. A frequency of 24% was found for the TNF2 patients with neuropsychiatric involvement and was not statistically different to a frequency of 28% found in SLE patients without neuropsychiatric manifestations. The TNF-2 allele does not confer susceptibility for neuropsychiatric manifestations in SLE patients.