TAS2R60 – Alzheimer disease

This summary evaluates the association of TAS2R60 (HGNC:20639) with Alzheimer disease (MONDO_0004975) as derived from recent multi‐patient genetic studies and functional assessments. Multiple genome‑wide association studies (GWAS) in cohorts of African Americans have identified several SNPs robustly associated with altered TAS2R60 expression, suggesting that disruptions in taste receptor gene regulation may contribute to Alzheimer disease risk (PMID:39284855, PMID:39372803).

The overall clinical validity is rated as Moderate. This classification is supported by the reproducible identification of three SNPs across four independent GWAS studies and significant eQTL signals in large cohorts (n = 475 subjects PMID:39284855), although no classical familial segregation data are available. The genetic evidence for TAS2R60 relies on statistical associations rather than Mendelian segregation patterns.

Genetic evidence indicates a complex model of inheritance where alterations in TAS2R60 expression are linked to Alzheimer disease risk. While familial aggregation is not demonstrated (affected relatives: 0), the findings are bolstered by the consistent detection of SNPs associated with down‑regulation of TAS2R60. No specific coding variants in HGVS nomenclature (starting with “c.” and including a corresponding “(p…)” annotation) were reported in the provided data.

Functional studies have been conducted on a panel of bitter taste receptors including TAS2R60. However, direct experimental assays demonstrating a causal role for TAS2R60 in Alzheimer disease are lacking. The available functional data primarily stem from receptor assays performed on closely related receptors, with the evidence for TAS2R60 being indirectly inferred from its co‐regulation with TAS2R41 (PMID:23632330). As such, the experimental support for the pathogenic mechanism related to TAS2R60 in Alzheimer disease is considered limited.

In summary, while robust genetic associations support a moderating role for TAS2R60 in Alzheimer disease pathogenesis, the absence of direct functional studies limits the overall evidentiary strength. The combination of replicated GWAS signals with significant eQTL associations provides a moderate level of confidence in the genetic link, although further targeted functional assays are necessary.

Key take‑home message: TAS2R60 represents a promising candidate gene for Alzheimer disease, with considerable genetic evidence suggesting its involvement, yet additional functional validation is required to fully establish its clinical utility.

References

• Scientific Reports • 2024 • Genomic study of taste perception genes in African Americans reveals SNPs linked to Alzheimer's disease PMID:39284855
• bioRxiv • 2024 • Genomic Study of Taste Perception Genes in African Americans Reveals SNPs Linked to Alzheimer's Disease PMID:39372803
• Biochemical and biophysical research communications • 2013 • Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol PMID:23632330

Evidence Based Scoring (AI generated)