Dried Blood Spot-Based Quantification Indicates Correlation Between lncRNA GAS5, Diabetes, Age, and War Eras in US Veterans.

US Veterans are disproportionately affected by type 2 diabetes (T2D) compared with civilians. Previously, we demonstrated that serum GAS5 levels are lower in Veterans with T2D compared with non-diabetics and established GAS5 as a genetic biomarker for T2D, validated by others. Dried blood spots (DBS) are advantageous because collection is minimally invasive, and shipment can be at room temperature. Measurement of lncRNAs in DBS is not yet reported and hence we sought to measure lncRNA GAS5 levels in DBS collected from Veteran participants. Results demonstrate that older age was independently associated with lower GAS5 levels among Veterans. Comparing Veterans across war eras, in this cohort, Vietnam War (VW) Veterans had higher incidences of diabetes compared to Gulf War (GW) or Other (non-VW/GW) wars. VW Veterans with A1c values greater than 6.5 had lower GAS5 levels, independent of BMI. Among the VW Veterans, a very small number of Veterans with self-reported Agent Orange (AO) exposure had lower GAS5 levels. Based on this observation, a mouse model with acute TCDD exposure was evaluated for Gas5 levels. The results demonstrate a significant negative correlation between TCDD dose and Gas5 levels measured in blood and DBS in the mouse model. Overall, the study demonstrates that lncRNA GAS5 measured in DBS and blood may be used in biomarker studies in diabetic patients. These results support the use of DBS in longitudinal studies of chronic diseases in active-duty service members or Veterans with toxic exposures during military service.