Association of HLA-DRB1 polymorphism with Alzheimer’s disease: a replication and meta-analysis

Abstract

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.