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Association of Small Ubiquitin-related Modifier 3 Gene Polymorphisms with Alzheimers disease in Korean Population

Author(s): Min-Seon Kim, Myung-Jin Mun, Jin-Ho Kim, Ji-Young Choi, Seung-Hun Jeon, Sue Kyung Kim, Jung Jae Lee, Seok Bum Lee, Won-Cheoul Jang


Background:  Sumoylation is an important post-translation modification that regulates various cellular pathways where small ubiquitin-related modifiers (SUMOs) are covalently linked to lysine residues of cellular target proteins. SUMO has proven to be linked to neuronal development and associated
with pathogenesis of Alzheimer’s disease (AD). Among the SUMO family, SUMO1 and 2 gene polymorphisms were significantly associated with risk of AD. However, genetic study of SUMO3 gene in AD has not been reported yet.

Methods: The association between SUMO3 gene polymorphisms and risk of AD was investigated in Korean population consisted of 144 AD patients and 329 healthy controls. The five tag SNPs within the SUMO3 gene were selected based on observed linkage disequilibrium (LD) and were used for
genotyping. In this case-control study, statistical analysis using logistic regression evaluated to odds ratio (OR) and 95% confidence interval (95% CI) for the relationship between these polymorphisms and risk of AD.

Results:  The CT genotype of rs235337 was significantly associated with a decreased risk of AD (OR: 0.455, 95% CI: 0.211-0.979, p-value: 0.044) in female group. In contrast, the rs2838694 GG genotype was related with a highly increased risk of AD (OR: 26.88, 95% CI: 1.197-603.5, p-value: 0.038) in female group. After conducting subgroup analysis of the selected five tag SNPs using Apolipoprotein E (ApoE) ε4 status, the CT genotype of rs235337 with a decreased risk of AD (OR: 0.355, 95% CI: 0.153- 0.827, p-value: 0.016), and the GG genotype of rs2838694 with a highly increased risk of AD (OR:
36.71, 95% CI: 1.579-853.3, p-value: 0.025) were investigated in the ApoE ε4 non-carrier group. In ApoE ε4 carrier status, all tag SNPs were not associated with a risk of AD.

Conclusion:  This is a case-control genetic association study to investigate whether the risk of AD is linked to SUMO3 polymorphisms in a Korean population. The two tag SNPs, rs235337 and rs2838694, within the SUMO3 gene showed that they have potential genetic risk factors for AD in a Korean
population. Furthermore, investigation of genetic association study will be useful to determine the true susceptibility of SUMO3 polymorphism to AD.

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