Mutation screening of the interferon-gamma gene as a candidate gene for multiple sclerosis

Interferon-gamma (IFN-gamma) plays a crucial role in the regulation of the immune response. Alterations in IFN-gamma production have been found in sev eral diseases including multiple sclerosis (MS). Such alterations could be caused by the action of different factors on cytokine production, or, theor etically, by mutations in the gene. We screened the IFN-gamma gene promoter and part of the first intron, known to contain a c-Rel specific enhancer, for possible mutations by sequencing. We found a C to T substitution in the IFN-gamma promoter at position -333. Screening for this mutation by sequen ce-specific PCR in 214 MS patients and 164 controls identified two patients , both heterozygous, but no controls with this mutation. No mutations were found in the first intron. The interferon-gamma gene is highly conserved an d changes in IFN-gamma expression are probably due to the influence of regu latory factors on gene transcription, rather than gene polymorphisms.