A Missense Variant in TREML2 Reduces Risk of Alzheimer's Disease in a Han Chinese Population.

Recently, Benitez and colleagues re-analyzed whole-exome sequencing data and revealed that a coding missense variant (rs3747742-C) in triggering receptor expressed on myeloid cells-like 2 (TREML2) gene reduced late-onset Alzheimer's disease (LOAD) risk in Caucasians. To date, no study was carried out to test this association in other ethnic groups and populations, including Han Chinese. Therefore, the aim of the current study was to validate the relation between rs3747742 and LOAD susceptibility in a large Han Chinese population including 992 LOAD patients and 1358 healthy controls. In the total sample, the minor (C) allele of rs3747742 was associated with a reduced LOAD risk under the recessive genetic model after Bonferroni correction (odds ratio (OR) = 0.713; 95 % confidence interval (CI): 0.546-0.932; P = 0.013, Bonferroni-corrected P = 0.039). Interestingly, after stratifying data according to apolipoprotein E (APOE) ε4 status, we revealed that this protection only exists in APOE ε4 carriers (recessive genetic model, OR = 0.448; 95 % CI: 0.262-0.765; P = 0.003, Bonferroni-corrected P = 0.009) in our cohort. Taken together, our findings support rs3747742-C as a protective factor for LOAD, especially in APOE ε4 carriers.

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