PRKAB2 and Type 2 Diabetes Mellitus

Two independent large‐scale association studies have rigorously evaluated the role of PRKAB2 (HGNC:9379) in type 2 diabetes mellitus (MONDO_0005148). In a study involving 149 diabetic cases with early onset and matched controls (PMID:12490143), a screening of variants (including several intronic SNPs and one rare 4 bp insertion/deletion) in PRKAB2 revealed no significant difference between cases and controls. This lack of association was confirmed in a subsequent haplotype analysis of 4,206 individuals (PMID:16505254), where neither single‐marker nor multi‐marker tests supported a link between PRKAB2 variants and type 2 diabetes mellitus or related metabolic traits.

While functional studies in a cancer context have indirectly noted that PRKAB2 is modulated via the AMPK pathway following nutrient deprivation—suggesting potential metabolic consequences (PMID:28475405)—these experiments were conducted in models of tumor biology and do not directly support a pathogenic mechanism in type 2 diabetes mellitus. Taken together, the genetic evidence refutes a role for PRKAB2 variants in the susceptibility to type 2 diabetes mellitus, and thus, based on current data, this gene-disease relationship is not clinically actionable.

References

• Molecular and Cellular Probes • 2002 • Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians PMID:12490143
• Diabetes • 2006 • Haplotype structures and large-scale association testing of the 5' AMP-activated protein kinase genes PRKAA2, PRKAB1, and PRKAB2 [corrected] with type 2 diabetes PMID:16505254
• Cancer Biology & Therapy • 2017 • The codon 72 polymorphism of p53 influences cell fate following nutrient deprivation PMID:28475405

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