Journal article

Binding of Gtf2i-beta/delta transcription factors to the ARMS2 gene leads to increased circulating HTRA1 in AMD patients and in vitro

Yang Pan, Daisuke Iejima, Mao Nakayama, Akiko Suga, Toru Noda, Inderjeet Kaur, Taraprasad Das, Subhabrata Chakrabarti, Robyn H Guymer, Margaret M DeAngelis, Megumi Yamamoto, Paul N Baird, Takeshi Iwata

JOURNAL OF BIOLOGICAL CHEMISTRY | ELSEVIER | Published : 2021

Abstract

The disease-initiating molecular events for age-related macular degeneration (AMD), a multifactorial retinal disease affecting many millions of elderly individuals worldwide, are still unknown. Of the over 30 risk and protective loci so far associated with AMD through whole genome-wide association studies (GWAS), the Age-Related Maculopathy Susceptibility 2 (ARMS2) gene locus represents one of the most highly associated risk regions for AMD. A unique insertion/deletion (in/del) sequence located immediately upstream of the High Temperature Requirement A1 (HTRA1) gene in this region confers high risk for AMD. Using electrophoretic mobility shift assay (EMSA), we identified that two Gtf2i-β/δ t..

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Grants

Awarded by Japan Agency for Medical Research and Development


Awarded by Japan Society for the Promotion of Science (JSPS)


Awarded by National Health and Medical Research Council of Australia (NHMRC)


Funding Acknowledgements

This work has been supported by research grant to T. I. by the Japan Agency for Medical Research and Development (19ek0109282h0003), T. I. by the Bilateral Program (2006-2007), Japan Society for the Promotion of Science (JSPS, 963552) with (D. B. and I. K.). Under the Bilateral Program (2006-2007), Department of Science & Technology and Australia-India Strategic Research Fund (AISRF) jointly funded through the Department of Biotechnology (DBT), Government of India (S. C. and I. K.) and the Department of Innovation, Industry, Science and Research (DIISR), Government of Australia (P. N. B. and R. H. G.). National Health and Medical Research Council of Australia (NHMRC) Research Fellowship 1138585 (P. N. B.) and 1103013 (R. H. G.). I. K. and S. C. would acknowledge the support of Retina consultants of LVPEI; Dr Nazimul Hussain, Dr Avinash Pathengay, Late Dr Annie Mathai and Dr Anjli Hussain for their help in recruitment of AMD patients and controls for this study. CERA receives Operational Infrastructure Support from the Victorian Government, Australia.