rs2266788

This functional study demonstrates that the GDF15 3' UTR variant rs1054564 (G>C) results in allele-specific translational repression of GDF15 by microRNA hsa-miR-1233-3p and hsa-miR-873-5p. Using bioinformatics prediction and in vitro luciferase reporter assays in HEK293T and A2058 melanoma cells, the authors show that the rs1054564-G allele creates stronger miRNA binding sites (lower free energy), leading to significantly decreased luciferase activity (P<0.05). Western blots confirmed that transfection of both miRNA mimics significantly decreased endogenous GDF15 expression (P<0.05), with hsa-miR-1233-3p showing significant allele-specific differences (P=0.034).

This review examines 15 years of ischemic stroke susceptibility gene research, organized into three periods: early candidate gene studies (1985-1995) testing variants in hemostasis and homocysteine metabolism genes; expansion period with functional variants discovered from other diseases tested on larger stroke cohorts; and current GWAS-driven large-scale genotyping studies. Key findings include identification of susceptibility loci in CELSR1 (rs6007897, rs4044210 in Japanese populations), PITX2 (rs2200733, rs10033464), and other genes involved in lipid metabolism (APOA5, APOCIII, MLXIPL) and signal transduction (PDE4D, ALOX5AP), with evidence that alleles are often shared across diseases and that careful clinical stratification is critical.