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PDK4 and Abdominal Obesity-Metabolic Syndrome

Recent multi‑patient studies have examined the association between PDK4 (HGNC:8812) and abdominal obesity‑metabolic syndrome (MONDO_0000816). In a Korean cohort of 651 probands (PMID:22019269) and 350 controls, common polymorphisms in PDK4 were evaluated. Although a modest association of a specific haplotype (ACAGC) with metabolic syndrome was initially observed, significance was lost after adjustment for multiple comparisons (PMID:22019269). No familial segregation data or reliable variant‐specific pathogenicity has been reported, further limiting the strength of the genetic association.

The functional evidence supporting a direct mechanistic link between PDK4 and abdominal obesity‑metabolic syndrome is also limited. While PDK4 is known to regulate glucose utilization and lipid metabolism, there is insufficient experimental data in disease‑relevant models to confirm a causative role. Overall, the cumulative evidence supports a limited gene‑disease association, underscoring the need for further studies before PDK4 findings can be confidently applied in diagnostic or therapeutic decision‑making.

References

  • Diabetes research and clinical practice • 2012 • Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome PMID:22019269
  • PLoS one • 2017 • DNA methylation of candidate genes in peripheral blood from patients with type 2 diabetes or the metabolic syndrome PMID:28727822

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Large cohort studies including 651 probands (PMID:22019269) showed at most a modest haplotype trend that did not withstand correction, with no segregation data available.

Genetic Evidence

Limited

Association studies of common PDK4 polymorphisms yielded inconclusive results with no robust genotype‐phenotype correlations or segregation data.

Functional Evidence

Limited

While PDK4 is mechanistically implicated in glucose and lipid metabolism, experimental evidence in models relevant to abdominal obesity‑metabolic syndrome is lacking.