TREM2 R47H variant and risk for Alzheimer’s disease: assessment in a Greek population and updated meta-analysis

Abstract

Introduction

Rare coding variants in TREM2 and their association with the susceptibility towards Alzheimer’s disease (AD) were recently studied in various ethnic groups with contradictory results. The T allele of the rs75932628 (p.R47H variant) has shown a positive risk association with AD in several studies; however, neither a study in Greece nor an updated meta-analysis have been conducted.

Objective

To assess the association between TREM2 rs75932628 and late-onset (sporadic) AD in a Greek population, and perform a meta-analysis of current data.

Materials and Methods

The rs75932628 was genotyped in a total of 327 patients with AD and 700 cognitively healthy controls. A systematic search and meta-analyses of studies presenting data regarding rs75932628 in AD cases and controls were also performed.

Results

Three patients vs. none of the controls were found to carry the heterozygous risk allele of the rs75932628, yielding a significant association (p = 0.032), in the Greek sample. In the meta-analysis, the overall odds ratio (OR) under a fixed-effects model was 2.98 (Confidence Interval (CI):2.52–3.53) showing a significant association of the rs75932628-T allele with AD in the overall dataset, based on data from 27 studies (26200 AD cases and 142084controls). Caucasian population-only studies (n = 16) revealed a similar OR of 2.93 (CI:2.45–3.51), whereas Asian population-only studies (n = 5) had a non-significant OR of 0.84 (CI:0.19–3.74).

Conclusion

The rs75932628 was associated with AD in the Greek sample. Our meta-analysis, covering a total population of over 168,000 people, also showed a significant association of the allele with AD in Caucasian populations.

Keywords:

• Alzheimer disease
• genetics
• single-nucleotide polymorphism
• TREM2
• meta-analysis
• rs75932628
• R47H

Disclosure statement

No potential conflict of interest was reported by the authors.

Informed consent

Informed consent was obtained from all individual participants (or their close relatives) included in the study.

Additional information

Funding

This study was supported in part by a research grant from the Research Committee of the University of Thessaly, Greece (code: 5287). The study was also supported by a grant from the Alexander Onassis Public Benefit Foundation to one of the authors, Alexios-Fotios A. Mentis. The Foundation played no role in this study’s design or writing of manuscript.