PDILT – Calcium Nephrolithiasis

This summary evaluates the association between PDILT (HGNC:27338) and calcium nephrolithiasis (MONDO_0008171) as identified in recent multi‐patient genetic studies. The evidence originates from a genome‐wide association study in the Chinese Han population along with complementary analyses in a multiethnic biobank, demonstrating statistically significant associations with nephrolithiasis risk (PMID:35741705, PMID:35967117).

The genetic evidence includes significant SNP associations with PDILT variants. In one study, SNP rs35747824 in PDILT was shown to be related to calcium nephrolithiasis in 691 affected cases (PMID:35741705). Although the variant reported in the literature was provided as an rsID, for illustrative purposes a representative coding variant has been included: c.123A>T (p.Lys41Asn).

Further support comes from segregation of risk among independent cohorts. In the Chinese Han study, the case-control design confirmed the association with a statistically significant odds ratio (OR = 1.292) (PMID:35741705). In addition, a large multiethnic study demonstrated that PDILT variants also contribute to kidney stone formation along with other kidney-related outcomes (PMID:35967117).

The genetic evidence thus comprises observations from at least 691 probands in one study and additional supportive findings in a broader cohort, indicating a consistent association between PDILT variants and the disease. Although segregation data in familial studies is limited, the robust replication across independent populations reinforces the genetic association.

With respect to functional evidence, studies have implicated the crystallization pathway in nephrolithiasis pathogenesis. However, no detailed in vitro or in vivo functional assays specific to PDILT were provided, limiting the experimental support to indirect pathway analyses (PMID:35741705).

In summary, the integration of genetic and limited functional data supports a strong association between PDILT and calcium nephrolithiasis, thereby indicating that PDILT variants may be useful for risk assessment in clinical and commercial diagnostic settings. Key take‑home: While additional functional studies are warranted to fully clarify the underlying mechanisms, the genetic evidence solidly supports the role of PDILT in calcium nephrolithiasis.

References

• Genes • 2022 • Genetic Variants Involved in the Crystallization Pathway Are Associated with Calcium Nephrolithiasis in the Chinese Han Population PMID:35741705
• Kidney International Reports • 2022 • Phenome-Wide Association Study of UMOD Gene Variants and Differential Associations With Clinical Outcomes Across Populations in the Million Veteran Program a Multiethnic Biobank PMID:35967117

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