KAZN – Endometriosis

The association between KAZN and endometriosis is supported by two independent genetic studies that evaluated both common and rare variants in diverse cohorts. One study assessed 394 infertile women with endometriosis versus 650 fertile controls and identified a significant association of the KAZN rs10928050 SNP with endometriosis‑related infertility (PMID:30044155). A second study using whole‑exome sequencing in a deeply‐phenotyped cohort of 80 patients reported private KAZN variants in 8.8% of the subjects (PMID:37626618). Together, these investigations provide converging evidence for a genetic contribution of KAZN in the pathogenesis of endometriosis. The statistical associations observed suggest that KAZN may harbor both common susceptibility alleles and rare damaging variants. This multilayered genetic evidence underscores the potential clinical relevance of KAZN in this complex disease.

The genetic evidence further indicates a multifaceted variant spectrum, although detailed HGVS‐compliant variants have not been explicitly reported. The reported findings include common SNP associations as well as rare private variants that point to a contributory role of KAZN in endometriosis pathogenesis. Notably, the first study involved a sizable proband cohort of 394 cases (PMID:30044155), while the second study incorporated comprehensive whole‑exome sequencing of 80 patients (PMID:37626618). These data reflect a combination of case–control association and sequencing‐based rare variant analysis. Although no single HGVS variant meeting the strict criteria is provided, the overall variant landscape remains consistent with a contributory role in disease. Such evidence supports the use of KAZN screening as part of a broader genetic evaluation for endometriosis.

In terms of experimental evidence, no robust functional assays, animal models, or rescue experiments specific to KAZN in endometriosis have been reported. The proposed mechanism of pathogenicity is inferred indirectly from the gene’s biological function and its role in cell–cell adhesion and signaling, which may be perturbed in endometriosis. While the genetic association is compelling, the paucity of functional data limits the strength of the experimental evidence. Therefore, the functional evidence remains limited and supplementary to the genetic findings. Future studies with cellular or animal models will be crucial to elucidate the mechanistic link between KAZN alterations and the disease phenotype. As a result, current clinical assessments rely primarily on genetic association data rather than direct functional validation.

There is no strong evidence from segregation studies since familial data or additional affected relatives carrying segregating variants have not been adequately reported. The inheritance pattern in endometriosis appears to be complex, which is typical of multifactorial diseases involving multiple genes and environmental factors. Both studies utilize well‐powered case–control designs and sequencing approaches that collectively highlight the contribution of KAZN to disease risk. Although the evidence does not reach the threshold of a Mendelian inheritance model, the statistical associations remain significant and reproducible across independent analyses. The absence of detailed segregation data precludes a more definitive categorization, but the consistency across studies enhances confidence in the association. This integrated approach provides a meaningful basis for further investigation of KAZN in endometriosis.

In summary, the available data suggest a moderate clinical validity for the association between KAZN and endometriosis. The genetic evidence from a case–control study and a whole‑exome sequencing analysis support the contribution of KAZN variants to disease susceptibility, despite limited functional corroboration at this time. The collective findings indicate the involvement of both common and rare variants in the genetic architecture of endometriosis. Although additional functional and segregation data are needed, the current evidence is sufficient to consider KAZN as a candidate gene in the clinical evaluation of endometriosis. Clinicians may use these findings to guide further genetic testing and personalized risk assessment for patients with endometriosis‑related infertility.

Key Take‑home Sentence: The integration of statistical genetic evidence from independent cohorts underscores KAZN as a promising candidate gene for endometriosis, warranting its consideration in future diagnostic and therapeutic strategies.

References

• Gynecological endocrinology • 2019 • New candidate genes associated to endometriosis PMID:30044155
• Biomedicines • 2023 • Puzzling Out the Genetic Architecture of Endometriosis: Whole‑Exome Sequencing and Novel Candidate Gene Identification PMID:37626618

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