CTLA-4 in found to be involved in the pathogenesis of type 1 and 2 diabetes such as polymorphisms which affects the protein function that is relevant to the disease process. According to the previous research reports, CTLA-4 gene also been linked to a wide range of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, celiac disease, and primary biliary cirrhosis. Jaya et al., (2018) Type 1 diabetes mellitus (T1DM) is an organspecific autoimmune disease characterized by T cell-mediated destruction of pancreatic islets. The genetic factors involved consist of at least five vulnerability genes: Hence the objective of the study was to investigate for associations of CTLA-4 +49A/G polymorphisms with T1DM and T2DM using polymerase chain reaction and gene sequence analysis. The results found that the frequency distribution of CTLA4+49A/G genotype and alleles between T1DM, T2DM patients and normal controls were statistically significant. (OR 2.286; 95%CI 0.804 to 6.945; P=0.118), and the CTLA-4 +49A/G polymorphism was recognized as a risk susceptibility factor for T1DM and T2DM. The study concluded that significant association between CTLA-4 +49A/G polymorphism and T1DM and T2DM. So, the study suggested that the CTLA4 gene polymorphism is closely linked to the pathogenesis of diabetes. Further studies are necessary to investigate how genetic and environmental factors affect the pathogenesis of DM to provide a basis for early diagnosis, genotyping and treatment of DM.