Association of HLA-DRB1 polymorphism with Alzheimer's disease: a replication and meta-analysis.
Association of HLA-DRB1 polymorphism with Alzheimer's disease: a replication and meta-analysis.
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DOI：
10.18632/oncotarget.21479
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Tan L
中科院分区：
文献类型：
--
作者：
Lu RC;Yang W;Tan L;Sun FR;Tan MS;Zhang W;Wang HF;Tan L
全基因组关联研究（GWAS）已经确定HLA-DRB1中的一个单核苷酸多态性（SNP） rs9271192是白种人阿尔茨海默病（AD）的危险因素。rs9271192对AD的影响有待在其他民族队列中验证。为了评估HLA-DRB1 rs9271192多态性与中国北方汉族人群晚发型AD （LOAD）之间的关系，我们招募了982名LOAD患者和1344名性别和年龄匹配的健康对照。结果显示HLA-DRB1 rs9271192与LOAD相关（基因型P = 0.015，等位基因P = 0.04）。logistic回归结果显示，C等位基因纯合性显著增加了总样本在隐性模型下罹患LOAD的风险（P = 0.004, OR =2.069, 95% CI = 1.262 ~ 3.434）。将这些数据按载脂蛋白E (APOE) ε4状态分层，观察到的关联局限于APOE ε4非携带者（加性模型：P=0.048, OR =1.191, 95% CI =1.001 ~ 1.417；隐性模型：P < 0.001, OR = 2.601, 95% CI =1.519 ~ 4.566）。此外，敏感性分析后的meta分析证实，HLA-DRB1内的rs9271192增加了LOAD的风险（OR = 1.12, 95% CI = 1.08-1.15）。综上所述，HLA-DRB1 rs9271192中的C等位基因可能是LOAD的独立危险因素。
Genome-wide association studies (GWAS) have identified one single-nucleotide polymorphism (SNP) rs9271192 within HLA-DRB1 as a risk factor for Alzheimer's disease (AD) in Caucasians. The effect of rs9271192 on AD needed to be verified in other ethnic cohorts. In order to evaluate the association between HLA-DRB1 rs9271192 polymorphism and late-onset AD (LOAD) in the Northern Han Chinese population, we recruited 982 LOAD patients and 1344 sex- and age-matched healthy controls. The results showed that HLA-DRB1 rs9271192 was associated with LOAD (genotype P = 0.015, allele P = 0.04). The results of logistic regression revealed the C allele homozygosity strongly increased the risk of LOAD under a recessive model in the total sample (P = 0.004, OR =2.069, 95% CI = 1.262–3.434). When these data were stratified by apolipoprotein E (APOE) ε4 status, the observed association was confined to APOE ε4 non-carriers (additive model: P=0.048, OR =1.191, 95% CI =1.001–1.417; recessive model: P < 0.001, OR = 2.601, 95% CI =1.519–4.566). Furthermore, meta-analysis after sensitive analysis confirmed that rs9271192 within HLA-DRB1 increased the risk of LOAD (OR = 1.12, 95% CI = 1.08–1.15). To summarize, the C allele in HLA-DRB1 rs9271192 may be an independent risk factor for LOAD.
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影响因子：
3.7
作者：
Cruchaga C;Haller G;Chakraverty S;Mayo K;Vallania FL;Mitra RD;Faber K;Williamson J;Bird T;Diaz-Arrastia R;Foroud TM;Boeve BF;Graff-Radford NR;St Jean P;Lawson M;Ehm MG;Mayeux R;Goate AM;NIA-LOAD/NCRAD Family Study Consortium
通讯作者：
NIA-LOAD/NCRAD Family Study Consortium
影响因子：
4.4
作者：
Xia, Man;Yu, Jin-Tai;Tan, Lan
通讯作者：
Tan, Lan
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
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作者：
Xiao Q;Liu ZJ;Tao S;Sun YM;Jiang D;Li HL;Chen H;Liu X;Lapin B;Wang CH;Zheng SL;Xu J;Wu ZY
通讯作者：
Wu ZY
影响因子：
30.8
作者：
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通讯作者：
Amouyel, Philippe