摘要目的:探究类风湿关节炎（RA）患者还原型叶酸载体1（RFC1）基因多态性与甲氨蝶呤（MTX）疗效、血药浓度及不良反应的关系。方法:采用病例对照研究方法，收集2018年1月20日至2021年1月20日在商丘市第一人民医院行MTX治疗的268例RA患者，男性82例，女性186例，年龄（52.47±10.29）岁。检测其RFC1 G80A位点的基因型，检测初次服用MTX 48 h后的血药浓度，观察并统计治疗6个月后的疗效及不良反应。比较不同组别间RFC1 G80A位点基因型的差异，采用共线性诊断和logistic回归分析MTX疗效和血药浓度的影响因素。采用卡方检验比较不同基因型患者间不良反应的发生率。结果:RFC1 G80A位点基因型（GG/GA/AA）及基因频率（G/A）分布在有效组和无效组中的差异有统计学意义（ χ 2=6.583， P=0.037； χ 2=6.249， P=0.012），AA型治疗有效率59.26%（32/54）高于GG型36.49%（27/74）（ χ 2=6.516， P=0.011）；Logistic回归分析显示AA基因型患者相对于GG型的MTX治疗有效率的 OR（95% CI）值为2.491（1.206~5.144）。AA型患者的48 h血药浓度为1.15（0.75，1.35）μmol/L，与GG型［0.74（0.61，1.18）μmol/L］和GA型［0.84（0.69，0.99）μmol/L］相比，差异有统计学意义（ χ 2=7.152， P=0.028）。Logistic回归分析显示AA型患者48 h血药浓度较高的概率约为GG型的2.583（1.238~5.390）倍。肝功能损伤在3种不同基因型（GG/GA/AA）间的发生率差异有统计学意义（ χ 2=12.606， P=0.002）。 结论:RFC1 G80A位点多态性能够影响RA患者的MTX疗效、血药浓度及肝功能损伤，AA型患者相对GG型疗效更好、血药浓度较高，但肝功损伤率也更高。

abstractsObjective:To explore the relationship between reduced folate carrier 1(RFC1) gene polymorphism a curative effect, plasma concentration and adverse reaction of methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods:A total of 268 RA patients with 82 males and 186 females, aged (52.47±10.29) years, who received MTX treatment in the First People's Hospital of Shangqiu, from Jan 20, 2018 to Jan 20, 2021 were collected by case-control study. The genotype of RFC1 G80A locus were detected. The plasma concentration of MTX were detected after initial administration for 48 hours. The curative effect and adverse reactions were observed and counted after treatment for 6 months. The differences of RFC1 G80A genotype among different groups were compared. Collinearity diagnosis and logistic regression were used to analyze the influencing factors of MTX efficacy and plasma concentration. The incidences of adverse reactions among patients with different genotype were compared by Chi-square test.Results:The distribution of RFC1 G80A genotype (GG/GA/AA) and gene frequency (G/A) showed statistically significant differences between the effective group and the ineffective group (χ 2=6.583, P=0.037; χ 2=6.249, P=0.012), and the effective rate of AA type [59.26% (32/54)] was higher than that of GG type [36.49% (27/74)] (χ 2=6.516, P=0.011). Logistic regression analysis showed that the OR (95% CI) value of MTX response rate in AA genotype patients versus GG genotype patients was 2.491(1.206-5.144). The 48 hour plasma drug concentration of AA type patients was 1.15 (0.75, 1.35) μmol/L. Compared with GG type [0.74 (0.61, 1.18) μmol/L] and GA type [0.84 (0.69, 0.99) μmol/L], the difference was statistically significant(χ 2=7.152, P=0.028). Logistic regression analysis showed that the probability of high 48 hour plasma drug concentration in patients with AA type was approximately 2.583 (1.238-5.390) times higher than that in patients with GG type. There was a statistically significant difference in the incidence of liver function injury among three different genotypes (GG/GA/AA) (χ 2=12.606, P=0.002). Conclusion:RFC1 G80A locus polymorphism can affect the MTX efficacy, blood drug concentration and liver function damage in RA patients. AA type patients have better efficacy and higher blood drug concentration compared to GG type patients, but the rate of liver function damage is also higher.