Association of reduced folate carrier 1 gene polymorphism with methotrexate efficacy, plasma concentration and adverse reactions in patients with rheumatoid arthritis
10.3760/cma.j.cn114452-20230915-00143
- VernacularTitle:类风湿关节炎患者还原型叶酸载体1基因多态性与甲氨蝶呤疗效、血药浓度及不良反应的相关性
- Author:
Ming LI
1
;
Min ZHAO
;
Liangxue HOU
;
Peng JIAO
Author Information
1. 商丘市第一人民医院药学部，商丘 476000
- Keywords:
Arthritis;
Rheumatoid;
Methotrexate;
Reduced folate carrier 1;
Gene polymorphism
- From:
Chinese Journal of Laboratory Medicine
2024;47(3):278-285
- CountryChina
- Language:Chinese
-
Abstract:
Objective: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.
