MS4A基因区域遗传变异与基线认知、痴呆发生及认知进展的相关性研究OA
Association of genetic variants in the MS4A gene region with baseline cognition,dementia,and cognitive progression
目的 探讨跨膜4域亚家族A(MS4A)基因区域3个关键单核苷酸多态性(SNP)位点(rs7232、rs1582763、rs72918674)与基线认知功能以及长期痴呆发生和认知进展风险的关联.方法 本研究纳入来自阿尔茨海默病神经影像学倡议(ADNI)数据库中的2 430名受试者,具有rs7232、rs1582763和rs72918674基因型数据的受试者分别为1 136、809、809人.受试者具有来自ADNI数据库的认知功能相关量表和相关协变量的基线数据,以及纵向随访数据.采用多元线性回归分析3个SNP位点与基线认知量表的横向关联,采用Cox比例风险回归模型评估3个SNP位点对长期发生痴呆及认知进展结局的纵向关联.结果 在校正混杂因素后,rs7232与Rey听觉词语学习测验-学习得分(RAVLT-Learning)、逻辑记忆延迟回忆总分(LDELTOTAL)呈正相关,与Rey听觉词语学习测验-遗忘得分(RAVLT-F)、Rey听觉词语学习测验-遗忘百分比(RAVLT-PF)呈负相关(P<0.05).rs1582763与RAVLT-F、RAVLT-PF呈负相关,与数字符号替代测验得分(DIGITSCOR)呈正相关(P<0.05).rs7232(HR=0.752,P=0.007)与rs72918674(HR=0.808,P=0.048)可降低痴呆发生风险;rs7232(HR=0.748,P=0.018)和rs1582763(HR=0.760,P=0.034)可降低发生认知进展风险.结论 MS4A区域变异与横向认知功能及纵向痴呆、认知进展结局相关.其中rs7232表现出基线记忆保护与延缓痴呆及认知进展的双重保护效应;rs1582763主要作用于记忆遗忘与认知进展延缓;rs72918674表现出痴呆结局保护效应.
Objective To investigate the associations of three key single nucleotide polymorphism(SNP)loci(rs7232,rs1582763,rs72918674)in the MS4A gene region with baseline cognitive function and the long-term risks of de-mentia and cognitive progression.Methods A total of 2 430 participants from the Alzheimer's Disease Neuroimaging Ini-tiative database were included in this study,with 1 136,809,and 809 participants having genotype data for rs7232,rs1582763,and rs72918674,respectively.Participants had baseline data on cognitive function-related scales and rel-evant covariates,as well as longitudinal follow-up data from the database.Multiple linear regression was used to analyze the cross-sectional associations of the three SNP loci with baseline cognitive scales.Cox proportional hazards regression models were used to evaluate the longitudinal associations of the three SNP loci with long-term dementia and cognitive pro-gression outcomes.Results After adjusting for confounding factors,rs7232 was positively correlated with the Rey Audi-tory Verbal Learning Test-Learning score and Logical Memory Delayed Recall Total score,and negatively correlated with the Rey Auditory Verbal Learning Test-Forgetting score and Rey Auditory Verbal Learning Test-Percent Forgetting score(P<0.05).The rs1582763 was negatively correlated with Rey Auditory Verbal Learning Test-Forgetting score and Rey Auditory Verbal Learning Test-Percent Forgetting score,and positively correlated with the Digit Symbol Substitution Test score(P<0.05).The rs7232(HR=0.752,P=0.007)and rs72918674(HR=0.808,P=0.048)were associated with a re-duced risk of dementia;rs7232(HR=0.748,P=0.018)and rs1582763(HR=0.760,P=0.034)were associated with a reduced risk of cognitive progression.Conclusion Variants in the MS4A gene region were associated with cross-sectional cognitive function and longitudinal dementia and cognitive progression outcomes.Among these variants,rs7232 exhibited the dual effects of protecting baseline memory and de-laying dementia and cognitive progression,rs1582763 mainly affected memory forgetting and delayed cogni-tive progression,and rs72918674 showed a protective effect on dementia outcomes.
郎文娟;薛镕基;蔡涛;姜祖波;赵凤芝
青岛市市立医院神经内科,山东 青岛 266000青岛市和睦家医院重症医学科,山东 青岛 266000莱西市人民医院神经内二科,山东 青岛 266000青岛市市立医院疼痛科,山东 青岛 266000莱西市人民医院神经内二科,山东 青岛 266000
医药卫生
跨膜4域亚家族A单核苷酸多态性认知功能痴呆
MS4ASingle nucleotide poly-morphismCognitive functionDementia
《中风与神经疾病杂志》 2026 (9)
832-838,7
青岛市2024年度医疗卫生科研项目(2024-WJKY023)
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