Open Access

The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis

  • Authors:
    • Rong Li
    • Xia Wang
    • Pengfei He
  • View Affiliations

  • Published online on: February 11, 2021     https://doi.org/10.3892/etm.2021.9778
  • Article Number: 347
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rare variants in the coding sequence of triggering receptor expressed on myeloid cells 2 (TREM2) have been identified in Alzheimer's disease (AD). They have been reported to be causative or confer risk of AD in several populations. However, the results are not conclusive. Therefore, a meta‑analysis was performed to investigate the association between rare variants of TREM2 and the susceptibility to AD. Case‑control studies meeting the inclusion criteria were identified by searching the PubMed, Embase and Web of Science databases. The association between four commonly analyzed variants of TREM2, p.Arg47His (R47H), p.Arg62His (R62H), p.Asp87Asn (D87N) and p.His157Tyr (H157Y), and the risk of AD were evaluated by meta‑analyses with the fixed‑effects model. Finally, a total of 26 datasets comprising 28,007 cases and 45,121 controls were included. There was no or low between‑study heterogeneity in all comparisons. A significantly increased risk of AD was observed in carriers of R47H compared with non‑carriers [odds ratio (OR)=3.88, 95% CI: 3.17‑4.76, P<0.001], R62H (OR=1.37, 95% CI: 1.11‑1.70, P=0.004) and H157Y (OR=4.22, 95% CI: 1.93‑9.21, P<0.001). However, R62H only conferred a mild risk compared to R47H and H157Y (OR=1.37 vs. 3.88 and 4.22, respectively). D87N was not associated with AD susceptibility. Sensitivity analysis indicated that the association identified for R62H was not significant (P=0.192) when excluding a large‑sample study. Subgroup analysis according to ethnicity revealed significant associations (R47H and H157Y) in Caucasians but not in Asians. In conclusion, rare coding variants of TREM2 were associated with an elevated risk of AD, particularly in Caucasians.
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April-2021
Volume 21 Issue 4

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Spandidos Publications style
Li R, Wang X and He P: The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis. Exp Ther Med 21: 347, 2021
APA
Li, R., Wang, X., & He, P. (2021). The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis. Experimental and Therapeutic Medicine, 21, 347. https://doi.org/10.3892/etm.2021.9778
MLA
Li, R., Wang, X., He, P."The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis". Experimental and Therapeutic Medicine 21.4 (2021): 347.
Chicago
Li, R., Wang, X., He, P."The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis". Experimental and Therapeutic Medicine 21, no. 4 (2021): 347. https://doi.org/10.3892/etm.2021.9778