BET1L – Uterine Corpus Leiomyoma

BET1L has been implicated in the genetic susceptibility to uterine corpus leiomyoma based on multiple well‐powered genome‑wide association studies. The evidence comes from large-scale meta‑analyses that included over 21,804 imaging‑confirmed cases and more than 200,000 controls, thereby providing robust statistical support for the association (PMID:31249589). Several independent cohorts across different ancestries—including European and Asian populations—have replicated these associations, underscoring the broad relevance of BET1L in fibroid risk (PMID:23604678; PMID:23892540).

Genetic evidence primarily arises from statistically significant single nucleotide polymorphisms (SNPs) at the BET1L locus (for example, rs2280543 and rs12484776) that show consistent associations with both disease risk and fibroid characteristics. These variants have been identified in studies employing logistic regression models and meta‑analyses, with associations reaching genome‑wide significance across multiple ethnic groups (PMID:29743541).

While the detailed molecular mechanisms remain to be fully elucidated, the genetic data suggest that risk variants in BET1L may exert effects through regulatory mechanisms influencing gene expression. Some studies have noted that certain risk alleles serve as expression quantitative trait loci (eQTLs) in tissues relevant to fibroid pathogenesis, further supporting the gene’s role in the disease process (PMID:31249589).

The association studies conducted span diverse populations and involve large numbers of probands, which adds to the robustness of the findings. Although typical monogenic segregation data are not available for this complex trait, the replication across independent studies provides compelling indirect segregation evidence through consistent statistical associations.

It is noteworthy that detailed functional assays specifically addressing the role of BET1L in uterine leiomyoma are limited. Unlike classical functional studies in Mendelian disorders, the current body of work relies on eQTL analyses and bioinformatics predictions to infer a regulatory impact. Further studies aimed at dissecting the mechanistic basis of BET1L variants in fibroid development are warranted.

In summary, the considerable body of genetic evidence from multiple, large-scale studies supports a strong association between BET1L and uterine corpus leiomyoma. This association, despite minimal direct functional assessment, presents clinically relevant information that can aid in diagnostic decision‑making, guide commercial screening strategies, and inform future research publications.

Key Take‑home sentence: BET1L represents a robust genetic risk factor for uterine corpus leiomyoma, with multi‑ethnic evidence underscoring its potential clinical utility in risk assessment.

References

• Frontiers in Genetics • 2019 • A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids PMID:31249589
• Scientific Reports • 2018 • Association of BET1L and TNRC6B with Uterine Leiomyoma Risk and Its Relevant Clinical Features in Han Chinese Population PMID:29743541
• Human Genetics • 2013 • BET1L and TNRC6B Associate with Uterine Fibroid Risk among European Americans PMID:23604678
• Human Genetics • 2013 • Variants in BET1L and TNRC6B Associate with Increasing Fibroid Volume and Fibroid Type among European Americans PMID:23892540

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