Differential role of triggering receptors expressed on myeloid cells 2 R47H in 3 neurodegenerative diseases based on a systematic review and meta-analysis

BACKGROUND: Recent studies have suggested that the potential functional polymorphism R47H in triggering receptors expressed on myeloid cells 2 (TREM2) is associated with several neurodegenerative diseases, however, the results remain inconclusive. This meta-analysis aimed to investigate the association between TREM2 R47H and the risk for 3 typical neurodegenerative diseases: Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS: A literature review was carried out using PubMed, Medline, and Embase. Data analysis was conducted using Stata 15.0 software. The pooled odds ratio (ORs) and 95% confidence interval (CIs) were calculated. RESULTS: A total of 35 articles were identified as eligible: 22 on AD, 3 on ALS, 7 on PD, 2 on AD and ALS, and 1 on ALS and PD. The AD set included 23,092 cases and 30,920 controls, the ALS set included 7391 cases and 12,442 controls, and the PD set included 8498 patients and 9161 controls. We found that R47H was associated with an increased risk of AD in the total pooled population (P < .001, OR = 4.02, 95% CI = 3.15–5.13). However, this significant difference existed for Caucasian people (OR = 4.16, 95% CI = 3.24–5.33) but not for Asian or African people. Moreover, we did not find any significant differences in minor allele frequency distribution between the PD and control groups or between the ALS and control groups, not only for the total pooled population but also for the subgroups of different ethnicities. CONCLUSION: Our study suggested that R47H in the TREM2 gene leads to an increased risk for developing AD, but not for ALS and PD, which adds evidence to the notion that diverse pathogenesis may be involved in different neurogenerative diseases.