Guis Sandrine, Balandraud Nathalie, Bouvenot Julien, Auger Isabelle, Toussirot Eric, Wendling Daniel, Mattei Jean-Pierre, Nogueira Leonor, Mugnier Benedicte, Legeron Pierre, Landt Olfert, Serre Guy, Roudier Jean, Roudier Chantal
INSERM UMR 639 and Assistance Publique Hôpitaux de Paris, Hôpital de la Conception, Marseille, France.
Arthritis Rheum. 2007 Dec 15;57(8):1426-30. doi: 10.1002/art.23092.
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.
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.
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).
RA patients with a -308 G/G TNFalpha genotype respond to etanercept better than patients with a -308 A/G genotype.
确定肿瘤坏死因子α（TNFα）基因 -308 A/G多态性是否能像在接受英夫利昔单抗治疗的患者中观察到的那样，预测86例类风湿关节炎（RA）患者接受依那西普治疗的疗效。
采用聚合酶链反应和熔解曲线分析，使用特异性基因引物和探针，对86例接受依那西普治疗的RA患者进行 -308 A/G TNFα基因多态性基因分型。患者被分为A组（G/A基因型）和G组（G/G基因型）。我们使用28个关节疾病活动评分（DAS28）比较了6个月后A组和G组对依那西普的临床反应。经过12个月的治疗后，对86例患者中的48例再次进行评估。
86例患者中，18例（21%）属于A组，68例（79%）属于G组。治疗6个月后，A组55.6%的患者和G组82.4%的患者DAS28改善>1.2（卡方检验P = 0.027）。A组DAS28改善的平均值±标准差为1.69±1.31，G组为2.23±1.19（t检验P = 0.098）。治疗1年后，对48例患者再次进行检测：10例（21%）属于A组，38例（79%）属于G组。A组40%的患者和G组87%的患者DAS28改善>1.2（卡方检验P = 0.005）。A组DAS28改善的平均值±标准差为1.334±1.37，G组为2.29±1.47（曼-惠特尼U检验=115，P = 0.0057）。
TNFα基因 -308 G/G基因型的RA患者对依那西普的反应优于 -308 A/G基因型的患者。
