Relationship betweenmatrix metalloproteinase 2(MMP2)gene polymorphism and plasma concentration and efficacy of Donepezil hydrochloride in treatment of Alzheimer's disease(AD)
Objective To investigate the effects of matrix metalloproteinase 2(MMP2)gene single nucleo-tide polymorphism on serum concentration and therapeutic efficacy of donepezil hydrochloride in Alzhei-mer's disease(AD).Methods 97 cases of AD patients treated in the hospital from January 2020 to Janu-ary 2023 were selected as AD group,and 100 healthy elderly people who underwent physical examination during the same period were selected as healthy control group.All patients were admitted to the hospital to receive 5 mg/d of donepezil hydrochloride for 1 month and then the dose of donepezil hydrochloride was increased to 10 mg/d for 150 days.Mini-mental state examination(MMSE)was used to evaluate the cog-nitive function of the patients before and after treatment.The patients were divided into response group and non-response group according to whether the last MMSE score was decreased compared with the first MMSE score.After 6 months of thetreatment,the concentration of donepezil hydrochloride in the blood of the 2 groups was determined by high performance liquid chromatography-tandem mass spectrometry.The genotypes of MMP2 gene rs243865(C>T),rs2285053(C>T)in blood were detected by real-time quantitative polymerase chain reaction(PCR)and restriction fragment length polymorphism analysis.Results Compared with the healthy control group,the genotype distribution of MMP2 gene rs243865 and rs2285053 in the AD group showed no statistically significant difference in the genetic model of rs243865 locus(P>0.05),while the dominant model of rs2285053 locus showed a statistically significant difference(P<0.05).Af-ter the treatment with donepezil hydrochloride,compared with the non responsive group,the response group showed no statistically significant differences in the distribution of MMP2 gene rs243865 genotype,genetic model and implicit model(P>0.05),while the distribution of rs2285053 genotype,additive mod-eland explicit model showed statistically significant differences(P<0.05).There was no statistically sig-nificant difference in the blood concentration of donepezil hydrochloride among AD patients with different MMP2 gene loci rs243865 genotype(P>0.05).Compared with the TT genotype AD patients at the rs2285053 locus,the blood concentration of donepezil hydrochloride was increased in CC and CT genotype patients,and the difference was statistically significant(P<0.05).There was no statistically significant difference in the blood concentration of donepezil hydrochloride between the non responsive group and the responsive group(P>0.05).Conclusion The variation of rs2285053 locus of MMP2 gene is related to the serum concentration and efficacy of donepezil hydrochloride in the treatment of AD,which has certain guiding value for clinical treatment.
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