Multiple sclerosis and related disorders · 2021
Effect of inosine monophosphate dehydrogenase-1 gene polymorphisms on mycophenolate mofetil effectiveness in neuromyelitis optica spectrum disorder patients.
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Liu Lanzhi, Luo Zhaohui, Liu Fan, Shang Danqing, Qiu Dongxu, Jiao Xiao, Zhou Xiaoliang, Chen Si, Wu Junfang, Li Jing
Аннотация
BACKGROUND: Inosine monophosphate dehydrogenase-1 is the target of mycophenolate mofetil. This research investigated the association between the gene polymorphism of inosine monophosphate dehydrogenase-1 and effectiveness of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorder patients.
METHODS: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups.
RESULTS: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups. The genotypes C/C, C/T and T/T of rs2278294 (P = 0.031) also distributed differently between the two groups. Logistic regression analysis (adjusted by optic neuritis) showed that compared to the wild genotype C/C, C/T genotype had a 9-fold protection against relapse (OR=0.111 (0.022-0.548)), and T/T genotype had a 6.7-fold protection against relapse (OR=0.149 (0.026-0.854)).
CONCLUSION: Our study provides preliminary evidence that the genotype of rs2278294 is associated with the response of neuromyelitis optica spectrum disorder patients to mycophenolate mofetil therapy. And compared to wild allelic C, the mutation to T tended to respond better to MMF.
METHODS: Fifty-nine neuromyelitis optica spectrum disorder patients accepted Mycophenolate Mofetil therapy for 1 year at least were divided into two groups: relapsing (n=21) and non-relapsing (n=38). Four single-nucleotide polymorphisms (SNPs: rs2228075, rs2278294, rs2288550, and rs3793165) in the inosine monophosphate dehydrogenase-1 gene were detected. Then we analyzed the allelic frequencies and the genotypes of SNPs in two groups.
RESULTS: The allelic frequency of rs2278294 distributed differently between the relapse and non-relapsing patients (P=0.03), while no significant difference found in rs2228075, rs2288550 and rs3793165 between two groups. The genotypes C/C, C/T and T/T of rs2278294 (P = 0.031) also distributed differently between the two groups. Logistic regression analysis (adjusted by optic neuritis) showed that compared to the wild genotype C/C, C/T genotype had a 9-fold protection against relapse (OR=0.111 (0.022-0.548)), and T/T genotype had a 6.7-fold protection against relapse (OR=0.149 (0.026-0.854)).
CONCLUSION: Our study provides preliminary evidence that the genotype of rs2278294 is associated with the response of neuromyelitis optica spectrum disorder patients to mycophenolate mofetil therapy. And compared to wild allelic C, the mutation to T tended to respond better to MMF.