Polymorphism at position -308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis.

Abstract

To test whether the G-to-A polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNFalpha) gene influences response to infliximab therapy in patients with rheumatoid arthritis (RA). We genotyped 59 RA patients by polymerase chain reaction and subdivided them into two groups: those with the A/A or A/G genotype and those with the G/G genotype. We compared the groups' clinical responses to infliximab treatment after 22 weeks, using the Disease Activity Score in 28 joints (DAS28). We found that 42% of patients in the A/A and A/G group and 81% of patients in the G/G group had improvement of at least 1.2 in the DAS28 score (P = 0.0086). The average improvement in the DAS28 score was 1.24 in the A/A and A/G patients and 2.29 in the G/G patients (P = 0.029). These data suggest that patients with a TNFalpha -308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNFalpha -308 genotyping may be a useful tool for predicting response to infliximab treatment.