RRAD – Type 2 Diabetes Mellitus

This summary evaluates the association between RRAD (HGNC:10446) and type 2 diabetes mellitus (MONDO_0005148). Two independent case‑control studies have examined the potential link between a trinucleotide-repeat polymorphism at the rad locus and type 2 diabetes. In a 1995 study published in Diabetes, researchers identified a 10‑allele polymorphism (designated RAD1) and observed an excess of minor alleles among 210 NIDDM patients compared to 133 control subjects (PMID:7859947). This study also provided linkage data, mapping the rad locus to a 3‑cM chromosomal region, with significant logarithm of odds scores in informative families (PMID:7859947).

A subsequent 1999 study in Metabolism: Clinical and Experimental analyzed the RAD1 polymorphism in 115 Japanese patients with type 2 diabetes and 114 control subjects. Although the overall repeat length did not differ significantly between patients and controls, a statistically higher frequency of minor alleles (with five or three GTT repeats) was observed in diabetic patients (PMID:10024077). This finding supports a modest role for genetic variability at the rad locus in predisposition to type 2 diabetes in certain populations.

While the genetic evidence is derived from repeat polymorphism analysis rather than rare, high‑penetrance variants, the observed statistical associations in multiple cohorts contribute to a limited level of genetic evidence. No specific single‐nucleotide variant (e.g., an HGVS‑coded variant) was reported in these diabetes‐focused studies. Instead, the evidence is based on allele frequency differences rather than a defined causative mutation.

Functional studies on RRAD have largely focused on cardiac phenotypes such as congestive heart failure and Brugada syndrome; hence, there is a paucity of experimental work directly addressing the mechanistic impact of RRAD variation in type 2 diabetes. In the absence of diabetes‑focused functional assays, the mechanistic insight into how rad repeat variability might contribute to impaired insulin action or glucose metabolism remains speculative.

Integrating the available case–control data with the absence of supportive diabetes‑specific functional studies, the overall gene–disease association is categorized as Limited. This rating is based on evidence from two independent cohorts (totaling over 300 subjects across studies PMID:7859947, PMID:10024077) demonstrating modest allele associations, albeit with population‐specific variability and without robust segregation or functional corroboration.

Key Take‑home sentence: While RRAD shows a statistically significant association with type 2 diabetes in select populations, further mechanistic and replication studies are required to fully establish its clinical utility in diagnostic decision‑making.

References

• Diabetes • 1995 • Trinucleotide repeats at the rad locus. Allele distributions in NIDDM and mapping to a 3-cM region on chromosome 16q. PMID:7859947
• Metabolism: clinical and experimental • 1999 • Analysis of trinucleotide-repeat combination polymorphism at the rad gene in patients with type 2 diabetes mellitus. PMID:10024077

Evidence Based Scoring (AI generated)