Early studies examined the influence of HLA type on the side effect profile. Singal et al. (50) showed an increased prevalence of HLA-DR3 in patients with side effects from gold compared with patients without side effects, although Ten Wolde (51) and Alarcon (52) failed to replicate the association. Hakala et al. (53) suggested an increased prevalence of HLA-B40 in patients with gold pneumonitis. Stockman et al. (54) also found an association between proteinuria and HLA-DR3 and HLA-B8 and thrombocytopenia with HLA-A1 and HLA-DR4. Other genes within the major histocompatibility complex (MHC) have also been studied. One small study by Clarkson et al. (55) found that patients with the C4 null allele were more likely to develop side effects from either gold or D-Pa. Evans et al. (56) investigated the association between TNF microsatellite markers and gold intolerance and found that the haplotypes TNFa5b5 and TNFa6b5 had an increased risk of mucocutaneous side effects. These studies are suggestive of a role for gene(s) within the MHC in toxicity to gold, but this obviously requires further investigation.

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