Association of HLA-DRB1 polymorphism with Alzheimer’s disease: a replication and meta-analysis
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Rui-Chun Lu1, Wu Yang2, Lin Tan1, Fu-Rong Sun1, Meng-Shan Tan1, Wei Zhang1, Hui-Fu Wang1 and Lan Tan1
1Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
2International Department, The Affiliated Hospital of Qingdao University, Qingdao, China
Lan Tan, email: [email protected]
Keywords: Alzheimer’s disease, polymorphism, association study, HLA-DRB1, meta-analyses
Received: April 19, 2017 Accepted: September 20, 2017 Published: October 04, 2017
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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