AUTHOR=Fang Xinyu , Tang Wei , Yang Fuyin , Lu Weihong , Cai Jun , Ni Jianliang , Zhang Jiangtao , Tang Wenxin , Li Tao , Zhang Deng-Feng , Zhang Chen 

TITLE=A Comprehensive Analysis of the CaMK2A Gene and Susceptibility to Alzheimer’s Disease in the Han Chinese Population

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=11

YEAR=2019

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00084

DOI=10.3389/fnagi.2019.00084

ISSN=1663-4365

ABSTRACT=<p>There is ample evidence suggesting that calcium/calmodulin-dependent protein kinase II alpha (CaMK2A) may play an important role in the pathophysiology of Alzheimer’s disease (AD). This genetic study aimed to investigate whether <italic>CaMK2A</italic> confers susceptibility to the development of AD in the Han Chinese population. A total of seven single nucleotide polymorphisms (SNPs) within <italic>CaMK2A</italic> were screened in two independent cohorts from southwestern China (333 AD patients and 334 controls) and eastern China (382 AD patients and 426 controls) to discern the potential association between this gene and AD. In addition, a cross-platform normalized expression resource was used to investigate whether <italic>CaMK2A</italic> is differentially expressed in the brain between individuals with AD and the controls. In addition, expression quantitative trait loci (eQTL) analysis was used to explore the differences in <italic>CaMK2A</italic> expression in the brain among different genotypes. The cross-platform normalized data showed significant differences in <italic>CaMK2A</italic> expression in the hippocampus, entorhinal cortex and temporal cortex between the AD patients and the control subjects (|log FC| &gt; 0.1, <italic>P</italic> &lt; 0.05); however, only the differences in the hippocampus and temporal cortex remained after the multiple comparisons correction [false discovery rate (FDR)-corrected, <italic>P</italic> &lt; 0.05]. The frequency of the rs4958445 genotype was significantly different between the AD subjects and the controls from southwestern China (<italic>P</italic> = 0.013, <italic>P</italic> = 0.034 after FDR correction). When the two samples were combined, rs4958445 still showed a significant association with AD (<italic>P</italic> = 0.044). Haplotype analysis indicated that the T-A-C-A-T-C-C and T-G-C-A-T-C-C haplotypes in the southwestern cohort and the T-G-C-G-C-T-C haplotype in the eastern cohort, consisting of rs10051644, rs6869634, rs3797617, rs3756577, rs4958445, rs10515639 and rs6881743, showed a significant association with AD (<italic>P</italic> = 0.037, <italic>P</italic> = 0.026 and <italic>P</italic> = 0.045, respectively). Furthermore, the brain eQTL analysis revealed a significant association between the rs4958445 polymorphism and <italic>CaMK2A</italic> expression in the inferior olivary nucleus (<italic>P</italic> = 0.029). Our results suggest an important role for <italic>CaMK2A</italic> in the pathophysiology of AD in the Han Chinese population, especially the southwestern population.</p>