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  • Title: Influence of -308 A/G polymorphism in the tumor necrosis factor alpha gene on etanercept treatment in rheumatoid arthritis.
    Author: Guis S, Balandraud N, Bouvenot J, Auger I, Toussirot E, Wendling D, Mattei JP, Nogueira L, Mugnier B, Legeron P, Landt O, Serre G, Roudier J, Roudier C.
    Journal: Arthritis Rheum; 2007 Dec 15; 57(8):1426-30. PubMed ID: 18050183.
    Abstract:
    OBJECTIVE: To determine whether the -308 A/G tumor necrosis factor alpha (TNFalpha) gene polymorphism can predict the outcome of etanercept therapy in 86 patients with rheumatoid arthritis (RA), as already observed in patients treated with infliximab. METHODS: Eighty-six RA patients treated with etanercept were genotyped for -308 A/G TNFalpha gene polymorphism by polymerase chain reaction and melting curve analysis, using specific gene primers and probes. Patients were subdivided into group A (G/A genotype) and group G (G/G genotype). We compared clinical responses to etanercept between groups A and G after 6 months, using the Disease Activity Score in 28 joints (DAS28). After 12-month treatment, 48 of 86 patients were evaluated again. RESULTS: Of 86 patients, 18 (21%) belonged in group A and 68 (79%) belonged in group G. After 6-month treatment, 55.6% of patients in group A and 82.4% of patients in group G had DAS28 improvement >1.2 (P = 0.027 by chi-square). The mean +/- SD DAS28 improvement was 1.69 +/- 1.31 in group A and 2.23 +/- 1.19 in group G (P = 0.098 by t-test). After 1-year treatment 48 patients were tested again: 10 (21%) belonged in group A and 38 (79%) belonged in group G. Forty percent of patients in group A and 87% in group G had DAS28 improvement >1.2 (P = 0.005 by chi-square). The mean +/- SD DAS28 improvement was 1.334 +/- 1.37 in group A and 2.29 +/- 1.47 in group G (Mann-Whitney U test = 115, P = 0.0057). CONCLUSION: RA patients with a -308 G/G TNFalpha genotype respond to etanercept better than patients with a -308 A/G genotype.
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