Association and interaction of TOMM40 and PVRL2 with plasma amyloid- ? and Alzheimer?s disease among Chinese older adults: a population-based study

被引：23

作者：

Liang, Xiaoyan ^{[1
]}

Liu, Cuicui ^{[1
,2
]}

Liu, Keke ^{[1
,2
]}

Cong, Lin ^{[1
,2
]}

Wang, Yongxiang ^{[1
,2
]}

Liu, Rui ^{[1
]}

Fa, Wenxin ^{[2
]}

Tian, Na ^{[1
,2
]}

Cheng, Yingzhe ^{[2
]}

Wang, Nan ^{[1
]}

Hou, Tingting ^{[1
,2
]}

Du, Yifeng ^{[1
,2
]}

Qiu, Chengxuan ^{[1
,3
,4
]}

机构：

[1] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Neurol, Jinan, Shandong, Peoples R China

[2] Shandong First Med Univ, Dept Neurol, Shandong Prov Hosp, Jinan, Shandong, Peoples R China

[3] Stockholm Univ, Karolinska Inst, Dept Neurobiol, Aging Res Ctr, Stockholm, Sweden

[4] Stockholm Univ, Karolinska Inst, Ctr Alzheimer Res Care Sci & Soc, Stockholm, Sweden

来源：

NEUROBIOLOGY OF AGING | 2022年 / 113卷

基金：

瑞典研究理事会; 国家重点研发计划;

关键词：

Alzheimer?s disease; TOMM40; PVRL2; Gene -gene interaction; Plasma biomarkers; Population -based study; GENOME-WIDE ASSOCIATION; APOE LOCUS; RISK; CONTRIBUTES; VARIANTS; DEMENTIA; NETWORK; PICALM; BRAIN; BETA;

D O I：

10.1016/j.neurobiolaging.2021.12.013

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40 (rs2075650) and PVRL2 (rs6859) polymorphisms were detected using multiplepolymerase chain reaction amplification. Plasma A beta 40, A beta 42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73-22.48) for TOMM40 GG, 1.47 (0.89-2.42) for PVRL2 AA, and 12.87 (3.97-41.73) for having both risk alleles (P interaction = 0.0 0 03). Among APOE epsilon 3/ epsilon 3 carriers, the multiadjusted odds ratio of AD associated with TOMM40 AG was 2.90(1.15-7.31). In biomarker subsample, TOMM40 GG was significantly associated with lower plasma A beta 42 and the A beta 42-to-A beta 40 ratio ( p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing A beta metabolism.

引用

页码：143 / 151

页数：9

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