In their report on the genetics of methotrexate (MTX) related adverse effects, Berkun et al describe a high rate of 1298CC homozygosity among their patients with rheumatoid arthritis (RA) (24.7%) compared with the study group (12.8%).¹ They conclude that RA may be more common in the 1298CC homozygotes in their population, although conceding that this result may be biased by the cross sectional design of their study. Frequencies of the 1298C allele for Caucasian, Japanese, and African populations have been reported at 34, 21, and 9%, respectively,² placing the frequency of 24.7% in their patients with RA well within this range, questioning the influence of the 1298C allele on susceptibility to RA in this population.

The authors speculate that the protective effects of the 1298CC genotype on adverse events from MTX may be related to the absence of the 677T allele …