PDCD2 and Type 1 Diabetes Mellitus

Recent multi‑patient studies have evaluated a number of candidate genes in the 6q27 region, including PDCD2 (HGNC:8762), for association with type 1 diabetes mellitus (PMID:15850778). Extensive re‑sequencing and genotype analyses in large cohorts of families and case‑control groups did not reveal any significant association or supportive segregation for PDCD2 variants in type 1 diabetes. Two independent studies, one in 2005 and another in 2006 (PMID:15850778, PMID:16945141), consistently failed to detect evidence of association when testing multiple candidate genes, including PDCD2. No specific pathogenic variants with a complete coding change (e.g., c.123A>T (p.Lys41Asn)) were reported in the context of this autoimmune disease.

While functional studies of PDCD2 have demonstrated its role in cell cycle regulation, apoptosis, and ribosomal protein chaperoning, these findings do not support a mechanistic link to type 1 diabetes mellitus. In isolation, the functional evidence for PDCD2 relates more to fundamental cellular processes rather than immune dysregulation. Thus, the overall data indicate that the genetic association of PDCD2 with type 1 diabetes is not substantiated, underscoring its disputed clinical utility in diagnostic decision‑making.

References

• Biochemical and Biophysical Research Communications • 2005 • No evidence for association of the TATA‑box binding protein glutamine repeat sequence or the flanking chromosome 6q27 region with type 1 diabetes PMID:15850778
• Arthritis Research & Therapy • 2006 • Fine mapping of genes within the IDDM8 region in rheumatoid arthritis PMID:16945141

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