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This summary reviews the association between PLCD3 (HGNC:9061) and hypertensive disorder (MONDO_0005044). Two independent genome‑wide association studies provide the primary evidence for this association. In the first study, a large European cohort (34,433 subjects with replication in >90,000 additional individuals) demonstrated a significant association with blood pressure traits, reporting a p‑value of 1×10^-8 (PMID:19430483). The second study, conducted in a Japanese cohort of 1,279 subjects, also identified a modest association between PLCD3 and hypertensive disorder (PMID:22071413).
The genetic evidence is derived solely from common variant analyses. Although the association signal is statistically robust given the very large sample sizes, there is no Mendelian segregation data or definitive HGVS‐coded pathogenic variant available. As a result, no specific coding change—such as a variant in the format “c.123A>T (p.Lys41Asn)”—has been reported for PLCD3 in relation to hypertensive disorder.
Functional studies addressing PLCD3 have been performed in contexts unrelated to blood pressure regulation (for example, in alopecia and age‑related cataract models). Consequently, there is a lack of experimental evidence directly linking PLCD3 disruption to altered blood pressure or vascular dysfunction. This gap in functional data limits the current translational potential of the genetic findings, despite the significant statistical associations observed.
Overall, the gene‑disease association for PLCD3 in hypertensive disorder is best characterized as Limited. While replicated GWAS findings in large, multi‑ethnic cohorts underscore a statistically significant link, the absence of familial segregation evidence and direct functional validation for blood pressure regulation tempers its immediate clinical applicability.
Key take‑home: The association of PLCD3 with hypertensive disorder is statistically robust in large cohorts, yet its clinical utility as a diagnostic marker remains limited until further functional and mechanistic studies are undertaken.
Gene–Disease AssociationLimitedAssociation identified in two large-scale GWAS with significant p‑values (e.g., 1×10^-8) across multi‑ethnic cohorts, though lacking familial segregation and direct functional evidence (PMID:19430483, PMID:22071413). Genetic EvidenceLimitedCommon variant association signals in tens of thousands of subjects provide statistical support, yet no specific causal coding variant (HGVS formatted) has been identified. Functional EvidenceLimitedNo direct experimental studies have evaluated the role of PLCD3 in blood pressure regulation; available functional data pertain to unrelated phenotypes. |