Sumoylation regulates transcription factor transactivation, protein-protein interactions, and appropriate subcellular localization of certain proteins. Previous studies have shown that sumoylation of amyloid precursor protein (APP) is associated with decreased levels of amyloid beta (Aβ) proteins, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between polymorphisms of the SUMO genes and the risk of AD. Our study subjects consisted of 144 AD patients and 335 healthy controls without dementia. We focused on tagged single nucleotide polymorphisms (tagSNPs) of the SUMO1 and SUMO2 genes. The tagSNPs were amplified by PCR and sequenced. We used binary logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations between SUMO gene polymorphisms and the risk of AD. We found that rs12472035 polymorphism of SUMO1 was significantly associated with an increased risk of AD in male group (the CT genotype of rs12472035: adjusted OR=8.737, 95% CI=2.041-37.41, p-value=0.003). In addition, two polymorphisms of SUMO2 were significantly associated with an increased risk of AD in female group (the GA genotype of rs35271045: adjusted OR=2.879, 95% CI=1.399-5.924, p-value=0.004; and the TC genotype of rs9913676: adjusted OR=2.460, 95% CI=1.197-5.057, p-value=0.014). Furthermore, three combinations were associated with an increased risk of AD. Our data suggest that three individual polymorphisms and three combinations may be potential risk factors for AD in Korean population.