What Is Known and Objective Patients with optic neuritis (ON) have significant individual differences in their response to high-dose intravenous methylprednisolone (HIMP) therapy. This study aims to evaluate the association between gene polymorphisms and the efficacy of HIMP therapy in Chinese Han patients with ON mediated by aquaporin-4 immunoglobulin G antibody (AQP4-IgG) -positive neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS). Methods Chinese Han patients with AQP4-IgG(+) NMOSD-ON or MS-ON were genotyped for four candidate genes: ABCB1 (rs1045642, rs1128503, rs2032582), NR3C1 (rs41423247), TBX21 (rs9910408, rs16947078) and VDR (rs731236, rs1544410, rs7975232, rs2228570). Patients were divided into glucocorticoid resistance (GR) and glucocorticoid sensitivity (GS) groups based on vision acuity (VA) improvement after HIMP treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies and haplotype distributions. Results A total of 267 patients completed the follow-up, including 120 patients with AQP4-IgG(+) NMOSD-ON and 147 patients with MS-ON. We observed a significant association between the ABCB1 G2677T/A (rs2032582) polymorphism and glucocorticoid response in AQP4-IgG(+) NMOSD-ON patients. Changes in VA scores in patients with the GG genotype were significantly lower than those in patients with the T/A T/A genotype (1.07 +/- 1.20 vs. 1.77 +/- 1.31, p = 0.026). In the GS group, the G allele had a lower frequency than the T/A allele (32.03% vs. 60.16%, p = 0.001). Logistic regression analysis showed that the G2677T/A GG and G T/A genotypes could increase the GR risk 3.53 and 2.67 times compared with the T/A T/A genotype, respectively (OR = 3.534, 95% CI: 1.186-10.527, p = 0.023; OR = 2.675, 95% CI: 1.005-7.123, p = 0.049). In addition, haplotype analysis showed that AQP4-IgG(+) NMOSD-ON patients with the TAT/TTT haplotype (ABCB1 C3435T-G2677T/A-C1236T) were only 0.54 times more likely to develop GR than those with other haplotypes (OR = 0.542, 95% CI: 0.315-0.932, p = 0.026). However, we did not observe intergroup differences in the MS-ON population. What Is New and Conclusion Our findings suggest that the G > T/A polymorphism of ABCB1 G2677T/A and the TAT/TTT haplotype played a protective role in HIMP treatment of AQP4-IgG(+) NMOSD-ON but not MS-ON.
基金：
Foundation of Beijing Science and Technology Project [Z191100007619038]
第一作者机构：[1]Capital Med Univ, Natl Inst Drug Clin Trial, Beijing Tongren Hosp, 1 Dongjiaominxiang Rd, Beijing 100730, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Natl Inst Drug Clin Trial, Beijing Tongren Hosp, 1 Dongjiaominxiang Rd, Beijing 100730, Peoples R China[2]Capital Med Univ, Dept Neurol, Beijing Tongren Hosp, 1 Dongjiaominxiang Rd, Beijing 100730, Peoples R China[*1]National Institute for Drug Clinical Trial, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang Road, Beijing 100730, China.[*2]Department of Neurology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang Road, Beijing 100730, China.
推荐引用方式(GB/T 7714)：
Dai Yuyang,Ni Siyang,Wu Feng,et al.ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG-positive neuromyelitis optica spectrum disorder[J].JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS.2022,47(9):1379-1387.doi:10.1111/jcpt.13675.
APA：
Dai, Yuyang,Ni, Siyang,Wu, Feng,Guo, Shaojie,Zhao, Xiuli&Wang, Jiawei.(2022).ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG-positive neuromyelitis optica spectrum disorder.JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS,47,(9)
MLA：
Dai, Yuyang,et al."ABCB1 gene polymorphisms impact the effect of high-dose intravenous methylprednisolone therapy on optic neuritis associated with AQP4-IgG-positive neuromyelitis optica spectrum disorder".JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS 47..9(2022):1379-1387
