From evolutionary relics to diabetic mellitus sentinels: a Mendelian randomization study of endogenous retrovirus group V member 1

Human endogenous retroviruses (HERVs) are retroviral elements that have integrated into the human genome during evolution and have various effects on human health and disease.Diabetic mellitus (DM) is a common metabolic disorder that affects millions of people worldwide.The causal relationship between HERVs and DM is unclear and controversial.In the present study, we used Mendelian randomization (MR) to infer the causal effect of HERV group V member 1 envelope polyprotein (HERVV-1 Env) expression on three types of DM: type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM).We found that HERVV-1 Env expression had a significant protective effect on T1DM and GDM, albeit not on T2DM.The reverse MR analysis showed that the three subtypes of DM did not affect HERVV-1 Env expression.Our findings illuminate the intricate relationship between HERVV-1 Env expression and varying DM subtypes, highlighting distinct underlying mechanisms.This pioneering study into the potential causal ties between HERVs family members and DM onset offers a new perspective on the significance of HERVs in human health and pathology.