AB0009 Genetic association of mitochondrial dna polymorphisms with behÇet’s disease in a korean population

Background Behcet’s disease(BD) is an inflammatory multi-genetic disorder with unknown etiology. In the previous study, we sequenced whole mitochondrial nucleotides from blood of 20 BD patients and 10 sex-, age-matched healthy controls, m.248Au003eG, m.709Gu003eA, m.3970Cu003eT, m.6392Tu003eC, m.6962Gu003eA, m.10310Gu003eA, m.10609Tu003eC, m.12406Gu003eA, m.12882Cu003eT, m.13928Gu003eC, m.16129Gu003eA, and m16304Tu003eC were more frequently observed in patients group than healthy control without statistical significance. While, m.304Cu003eA, m.3010Gu003eA, m.4883Cu003eT, m.5178Cu003eA, and m.14668Cu003eT were more frequent in control group (p=0.008, 0.026, 0.007, 0.007, and 0.026, respectively). m.16182Au003eC, m.16183Au003eC, m.16189Tu003eC were associated with uveitis (p=0.041, 0.022, and 0.014, respectively). Objectives We performed a follow-up study to validate these possible associations in larger groups. Methods Whole blood or buffy coat were collected from 98 BD patients from four university hospitals located in Chung-Cheong district of Republic of Korea, 196 age-, sex-matched healthy controls from Konyang University Hospital. Above mentioned 20 targeted mitochondrial DNA(mtDNA) genomes were analysed using MassARRAY ® system(Agena Bioscience, Inc., San Diego, CA, USA) for m.709, m.3010, m.4883, m.6392, m.6962, m.10310, m.10609, m.12406, m.12882, m.13928, and m.14668; Sanger sequencing for m.248, m.304, m.5178, m.16129, m.16182, m.16183, m.16189, and m.16304; and TaqMan-based genotyping assay(Applied Biosystems, Foster City, CA, USA) for m.3970. Results were compared with the revised Cambridge Reference Sequence (rCRS). Chi square or Fisher’s exact test were used to analyse association of mtDNA alterations between groups and between mtDNA alterations and clinical/laboratory characteristics. Results Presence of m.248Au003eG, m.304Cu003eA, m.709Gu003eA, m.3010Gu003eA, m.3970Cu003eT, m.4883Cu003eT, m.5178Cu003eA, m.6392Tu003eC, m.6962Gu003eA, m.10310Gu003eA, m.10609Tu003eC, m.12406Gu003eA, m.12882Cu003eT, m.13928Gu003eC, m.14668Cu003eT, m.16129Gu003eA, and m16304Tu003eC were not differentiated by the groups. However, m.16812Au003eC was more frequently observed in the patient group than control [22 (22.4%) vs. 24 (12.2%), p=0.061], and it was significantly associated with HLA-B51 positivity (p = 0.011), arthralgia (p=0.043) and methotrexate use (p=0.02), and was not associated with uveitis in the follow-up study. Among clinical and laboratory characteristics in BD patients, thrombosis was more frequently observed in male patients than female patients [7 (22.6%) vs. 0 (0%), p Conclusions We performed a follow-up study to validate possible associations between BD and 20 mtDNA alterations. m.16812Au003eC could be associated with BD and its several clinical or laboratory characteristics a Korean population. References [1] Xavier JM, Shafiee NM, Ghaderi F, Rosa A, Abdollahi BS, Nadji A, et al. Association of mitochondrial polymorphism m.709Gu003eA with Behcet’s disease. Ann Rheum Dis2011;70:1514–6. [2] Kwon MH, Joung CI. Genetic Associations of Mitochondrial DNA Polymorphisms with Behcet’s Disease in a Korean Population: A Pilot Study. J Rheum Dis 2016;23(1):23–9. Acknowledgements The current study was supported by the National Research Foundation of Korea funded by the Korean Government (grant no. NRF-2017R1C1B2008199). Disclosure of Interest None declared