(HealthDay News) – A missense mutation in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) correlates with increased risk of Alzheimer’s disease, according to two studies published online Nov. 14 in the New England Journal of Medicine.

Thorlakur Jonsson, PhD, from deCODE Genetics in Reykjavik, Iceland, and colleagues identified sequence variations likely to affect protein variation in the genome sequences of 2,261 Icelanders and tested for an association with Alzheimer’s disease. The researchers found that the rare missense mutation rs75932628-T in TREM2, which was predicted to result in an R47H substitution, conferred a significant risk of Alzheimer’s disease (odds ratio, 2.92). The association was replicated in additional sample sets (odds ratio, 2.9 in discovery and replication samples combined). Compared with non-carriers, rs75932628-T carriers between the ages of 80–100 years without Alzheimer’s had poorer cognitive function.

In a second study, Rita Guerreiro, PhD, of the University College London, and colleagues analyzed the genetic variability in TREM2 in 1,092 patients with Alzheimer’s disease and 1,105 controls using genome, exome, and Sanger sequencing. The researchers identified significantly more variants in exon 2 of TREM2 among patients with Alzheimer’s disease compared with controls. The most common variant, rs75932628, was significantly associated with Alzheimer’s disease. This association was confirmed in a meta-analysis of rs75932628 genotypes imputed from genome-wide association studies and by direct genotyping of an additional patient series. Expression studies identified different expression of Trem2 in control mice and a mouse model of Alzheimer’s disease.

“Heterozygous variants in TREM2 are associated with a significant increase in the risk of Alzheimer’s disease,” the authors of the second study write.

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Several authors from both studies disclosed financial ties to the genomics and pharmaceutical industries.

Abstract – Jonsson
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Abstract – Guerreiro
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