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

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. To assess the association between TREM2 rs75932628 and late-onset (sporadic) AD in a Greek population, and perform a meta-analysis of current data. 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. Three patients vs. none of the controls were found to carry the heterozygous risk allele of the rs75932628, yielding a significant association (<i>p</i> = 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 (<i>n</i> = 16) revealed a similar OR of 2.93 (CI:2.45–3.51), whereas Asian population-only studies (<i>n</i> = 5) had a non-significant OR of 0.84 (CI:0.19–3.74). 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.

髓系细胞触发受体2（TREM2）的罕见编码变异及其与阿尔茨海默病（Alzheimer’s disease, AD）易感性的关联，近期在不同族群中被广泛研究，但所得结果存在矛盾。rs75932628（p.R47H变异）的T等位基因在多项研究中被证实与AD存在正向风险关联；然而，迄今尚未开展希腊人群相关研究，也未进行最新的荟萃分析。为探究希腊人群中TREM2 rs75932628与晚发性（散发性）AD的关联，并对现有数据开展荟萃分析，本研究共对327例AD患者与700例认知健康对照者进行了rs75932628的基因分型。同时，本研究还对报道了AD病例与对照者rs75932628相关数据的研究进行了系统检索与荟萃分析。在希腊人群样本中，共3例AD患者携带rs75932628的杂合风险等位基因，对照者中无此类携带者，这一结果提示二者存在显著关联（*p*=0.032）。在荟萃分析中，基于固定效应模型的合并比值比（OR）为2.98（置信区间（CI）：2.52~3.53），表明在纳入27项研究（共26200例AD患者、142084例对照者）的总数据集内，rs75932628-T等位基因与AD存在显著关联。仅纳入白种人群的研究（*n*=16）得到了相似的OR值2.93（CI：2.45~3.51），而仅纳入亚洲人群的研究（*n*=5）的OR值为0.84（CI：0.19~3.74），未达到统计学显著性。希腊人群样本中，rs75932628与AD存在显著关联。本研究的荟萃分析覆盖总人群超过16.8万，结果同样显示该等位基因与白种人群AD存在显著关联。