The genetic variation of ARRB2 is associated with late-onset Alzheimer's disease in Han Chinese.

Emerging evidence indicates that β-arrestin 2, an important regulator of G protein coupled receptors, is involved in the pathogenesis of Alzheimer's disease (AD). The aim of this study was to investigate the association between β-arrestin 2 gene (ARRB2) variation and the risk of late-onset AD (LOAD). A total of 1132 LOAD patients and 1158 healthy controls from the Han Chinese population were included in this study. Initially, four common single nucleotide polymorphisms (SNPs) (rs3786047, rs16954146, rs1045280 and rs2271167) were selected by consulting the Han Chinese from Beijing genotype data in HapMap database. Considering the fact that these four SNPs were located in one haplotype block and any two of them were in almost complete linkage disequilibrium (D'=1, r2≥0.897), we chose rs1045280 (a coding- synonymous variant) that covered all the common genetic variations in ARRB2 with r2≥0.8 as the tag SNP (tSNP) for the subsequent genotyping. Our results showed that the minor allele of rs1045280 was associated with an increased LOAD risk after adjusting for age, gender, educational level, and the apolipoprotein E (APOE) ε4 status under dominant (OR=1.291; 95% CI: 1.063-1.568; Bonferroni-corrected P=0.03) and additive (OR=1.269; 95% CI: 1.069-1.507; Bonferroni- corrected P=0.018) models. Meanwhile, when these data were stratified by APOE ε4 status, this association was evident only in APOE ε4 carriers (OR=1.617; 95% CI: 1.01-2.588; P=0.045). In summary, this study provide the first evidence that the tSNP of ARRB2 significantly increases LOAD risk in Han Chinese, suggesting ARRB2 may represent a susceptibility gene for LOAD.
AuthorsTeng Jiang, Jin-Tai Yu, Ying-Li Wang, Hui-Fu Wang, Wei Zhang, Nan Hu, Lin Tan, Lei Sun, Meng-Shan Tan, Xi-Chen Zhu, Lan Tan
JournalCurrent Alzheimer research (Curr Alzheimer Res) Vol. 11 Issue 4 Pg. 408-12 (May 2014) ISSN: 1875-5828 [Electronic] United Arab Emirates
PMID24635845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Apolipoprotein E4
  • Arrestins
  • beta-arrestin
  • Age Factors
  • Age of Onset
  • Aged
  • Alzheimer Disease (genetics)
  • Apolipoprotein E4 (genetics)
  • Arrestins (genetics)
  • Asian Continental Ancestry Group (genetics)
  • China
  • Educational Status
  • Female
  • Genetic Predisposition to Disease
  • Genotyping Techniques
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide
  • Sex Factors

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