Association Of IL-23R Gene With Lateonset Alzheimer’s Disease In A Northern Han Chinese Population

Background: Alzheimer’s disease(AD) is the most common neurodegenerative disorders in the aged people. However, the cause and pathogenic mechanism of AD is unclear yet. Chronic inflammation plays an indispensable role in AD. As reported by the researches upon animal models and human pathologic autopsy, there is lots of activated microglia around the degenerative neurons of the AD patients. These microglia could release many inflammatory factors including interleukin-1(IL-1),interleukin-6(IL-6),tumor necrosis factors-α(TNF-α), α1-antichymotrypsin(ACT) and et al. Recently, an interaction associated with the pathology of AD has been reported with the pro-inflammatory cytokines, interleukin-12(IL-12) and interleukin-23(IL-23). It is reported that inhibition of IL-23 signaling can reduce the AD pathology in Alzheimer’s disease-prone mice.Objectives: To evaluate the influences of IL-23 R gene single-nucleotide polymorphisms(SNPs) on the risk of lateonset Alzheimer’s disease(LOAD), a case-control study was conducted in Northern Han Chinese population.Methods: We conducted a case-control study to investigate the IL-23 R gene in 1133 patients diagnosed with LOAD and 1156 healthy participants matched for gender and age. The 2 functional SNPs, rs10889677(located in the 3′-UTR, A>C allele) and rs1884444(located at codon 3 of exon2, T>G allele, was genotyped using polymerase chain reaction–ligase detection reaction(PCR-LDR). Genotypes and alleles analyses were compared using the chi-square test and logistic regression.Results: For rs10889677, located at the 3′-UTR region, the allelic association analysis showed that the minor allele(C allele) at IL-23 R rs10889677 was associated with decreased risk of LOAD(Bonferroni-corrected P value= 0.048, OR=0.855, 95% CI=0.746-0.979). When adjusted for age, gender, and APOE ?4 status, the C allele still showed significant different in cases with controls, and decreased the risk of developing LOAD via additive model(OR=0.829, CI=0.720-0.955, Bonferroni-corrected minimum P=0.018) and dominant model(OR=0.720, 95%CI=0.595-0.870, Bonferroni-corrected P= 0.012) in APOE ?4 noncarriers. The G allele of rs1884444 polymorphism(OR=1.559, CI=1.175-2.068, Bonferroni-corrected minimum P=0.008) is associated with a higher risk of LOAD. Besides, our data showed the interaction of IL-23 R and APOE in the risk of LOAD.Conclusions: Our results suggest that the rs10889677 and rs1884444 polymorphisms of the IL-23 R gene may independently contribute to the risk of the LOAD. The C allele of rs10889677 can decrease the risk of LOAD, whereas the G allele of rs1884444 might increase the risk of LOAD.