The p.R47H Variant of TREM2 Gene is Associated With Late-onset Alzheimer Disease in Colombian Population

Arboleda-Bustos, Carlos E.; Ortega-Rojas, Jenny; Mahecha, María Fernanda; Arboleda, Gonzalo; Vásquez, Rafael; Pardo, Rodrigo; Arboleda, Humberto

doi:10.1097/wad.0000000000000275

Cited by 9 publications

(11 citation statements)

References 28 publications

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“…The authors concluded that TREM2 R47H could be an important LOAD risk factor, but more studies are necessary to corroborate the relationship described. 48 In Colombia, a recent study about LOAD genetics has also been performed. 49 It evaluated the association of 14 single-nucleotide polymorphisms in genes that have been connected to LOAD and confirmed this relationship through a genome-wide association study.…”

Section: Other Mutationsmentioning

confidence: 99%

“…In 2018, Arboleda-Bustos et al 48 studied the association between several TREM2 polymorphisms and LOAD. They found a relationship with the TREM2 arginine to histidine substitution at amino acid 47 ( R47H ) in a sample of 358 AD cases and 329 controls; specifically, this variant was identified in six LOAD probands: five (5/558 or 1.4%) heterozygous and one (1/358 or 0.28%) homozygous.…”

Section: Colombiamentioning

confidence: 99%

“…The authors concluded that TREM2 R47H could be an important LOAD risk factor, but more studies are necessary to corroborate the relationship described. 48 …”

Section: Colombiamentioning

confidence: 99%

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Genetics of dementia: insights from Latin America

Ramos

Aguillón

Cordano³

et al. 2020

Dement. neuropsychol.

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ABSTRACT. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are neurodegenerative disorders that result in a significant burden to both patients and caregivers. By 2050, the number of people with dementia in Latin America will increase 4-fold. A deep understanding of the relevant genetic factors of AD and FTD is fundamental to tackle this reality through prevention. A review of different genetic variants that cause AD or FTD in Latin America was conducted. We searched Medline and PubMed databases using the keywords “Alzheimer’s disease,” “frontotemporal dementia,” “mutation,” “America,” and “Latin America,” besides specific Latin American countries. Forty-five items were chosen and analyzed. PSEN1 mutations are the commonest cause of genetic early-onset Alzheimer’s disease (EOAD), followed by PSEN2 and APP mutations. Genetic FTD can be mainly explained by GRN and MAPT mutations, as well as C9orf72 G4C2 repeat expansion. APOE ε4 can modify the prevalence and incidence of late-onset Alzheimer’s disease (LOAD), in addition to the cognitive performance in affected carriers.

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Section: Other Mutationsmentioning

confidence: 99%

Section: Colombiamentioning

confidence: 99%

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Genetics of dementia: insights from Latin America

Ramos

Aguillón

Cordano³

et al. 2020

Dement. neuropsychol.

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“…Additional rare variants, including p.Arg62His (R62H, rs143332484), p.Asp87Asn (D87N, rs142232675) and p.His157Tyr (H157Y, rs2234255), have also been detected in AD subjects and indicated to increase the susceptibility to AD (11,12). Furthermore, certain TREM2 mutations, such as p.Gln33stop, p.Tyr38Cys and Thr66Met, have been identified only in patients with AD but not in normal controls, and appear to be causative (13), However, due to the low frequency of these variants, studies with a small sample size may not have adequate power to identify the genetic associations (14)(15)(16). The results of association studies from different regions and ethnicities are not always consistent.…”

Section: Introductionmentioning

confidence: 99%

The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis

Wang

2021

Exp Ther Med

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Rare variants in the coding sequence of triggering receptor expressed on myeloid cells 2 (TREM2) have been identified in Alzheimer's disease (AD). They have been reported to be causative or confer risk of AD in several populations. However, the results are not conclusive. Therefore, a meta-analysis was performed to investigate the association between rare variants of TREM2 and the susceptibility to AD. Case-control studies meeting the inclusion criteria were identified by searching the PubMed, Embase and Web of Science databases. The association between four commonly analyzed variants of TREM2, p.Arg47His (R47H), p.Arg62His (R62H), p.Asp87Asn (D87N) and p.His157Tyr (H157Y), and the risk of AD were evaluated by meta-analyses with the fixed-effects model. Finally, a total of 26 datasets comprising 28,007 cases and 45,121 controls were included. There was no or low between-study heterogeneity in all comparisons. A significantly increased risk of AD was observed in carriers of R47H compared with non-carriers [odds ratio (OR)=3.88, 95% CI: 3.17-4.76, P<0.001], R62H (OR=1.37, 95% CI: 1.11-1.70, P=0.004) and H157Y (OR=4.22, 95% CI: 1.93-9.21, P<0.001). However, R62H only conferred a mild risk compared to R47H and H157Y (OR=1.37 vs. 3.88 and 4.22, respectively). D87N was not associated with AD susceptibility. Sensitivity analysis indicated that the association identified for R62H was not significant (P=0.192) when excluding a large-sample study. Subgroup analysis according to ethnicity revealed significant associations (R47H and H157Y) in Caucasians but not in Asians. In conclusion, rare coding variants of TREM2 were associated with an elevated risk of AD, particularly in Caucasians.

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“…Mutations in the extracellular domain of TREM2 confer an elevated risk of developing late-onset AD. A risk allele (R47H) of TREM2 had an effect similar to ApoE4 (odds ratio 2.90-5.05) in a Colombian population 23 . TREM2 is a receptor expressed in macrophages including microglia in the brain.…”

Section: Microgliamentioning

confidence: 90%

Immunology of Alzheimer’s disease

Sosa-García¹,

Hernández-Jiménez²,

Moral-Huerta³

et al. 2019

RMN

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Alzheimer's disease (AD) is a multifactorial neurodegenerative pathology. Neuroinflammation is an early event of the presymptomatic stages in AD and contributes to its progression. We review the participation of astrocytes, microglia and blood-brain barrier cells, the mechanisms of cell death and the inflammatory factors such as chemokines, interferons and Toll-like receptors involved in progression and perpetuation of AD. Some of its prognostic and therapeutic possibilities are also mentioned. Identifying the different actors involved in inflammation and the main mechanisms of damage might allow the development of preventive strategies and treatments to fight against this devastating disease.

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The p.R47H Variant of TREM2 Gene is Associated With Late-onset Alzheimer Disease in Colombian Population

Cited by 9 publications

References 28 publications

Genetics of dementia: insights from Latin America

Genetics of dementia: insights from Latin America

The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta‑analysis

Immunology of Alzheimer’s disease

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