- Researchers have uncovered 16 genetic regions linked to diabetic kidney disease.
- The findings point to potential targets for prevention and treatment.
Newswise — Washington, DC (September 19, 2019) — In an unprecedented scale, researchers have begun to unravel the genetics that may predispose some individuals to develop kidney disease once they have diabetes, independent of the degree of blood sugar control. The findings appear in an upcoming issue of JASN.
Many individuals with type 1 diabetes develop kidney disease despite adequate blood sugar control, while others maintain normal kidney function despite long-term high blood sugar levels. Studies have shown that diabetic kidney disease (DKD) has a heritable component, but little is known about the genes involved.
To identify genetic variants that predispose people to DKD, Jose C. Florez, MD, PhD (Massachusetts General Hospital, Broad Institute, Harvard Medical School) and his colleagues completed genome-wide association analyses in 19,406 individuals of European descent with type 1 diabetes, with and without kidney disease. The researchers identified 16 novel gene regions linked to DKD, and they provided supportive biological data related to this link for some of them. For example, the team uncovered a variant at COL4A3, a gene that encodes a collagen protein that is important to kidney health.
“This study represents a substantial advance in the genetics of DKD, where previous studies had yielded few robust associations,” said Dr. Florez. “The 16 DKD-associated regions provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.”
Study co-authors include Rany M. Salem, Jennifer N. Todd, Niina Sandholm, Joanne B. Cole, Wei-Min Chen, Darrel Andrews, Marcus G. Pezzolesi, Paul M. McKeigue, Linda T. Hiraki, Chengxiang Qiu, Viji Nair, Chen Di Liao, Jing Jing Cao, Erkka Valo, Suna Onengut-Gumuscu, Adam M. Smiles, Stuart J. McGurnaghan, Jani K. Haukka, Valma Harjutsalo, Eoin P. Brennan, Natalie van Zuydam, Emma Ahlqvist, Ross Doyle, Tarunveer S. Ahluwalia, Maria Lajer, Maria F. Hughes, Jihwan Park, Jan Skupien, Athina Spiliopoulou, Andrew Liu, Rajasree Menon, Carine M. Boustany-Kari, Hyun M. Kang, Robert G. Nelson, Ronald Klein, Barbara E. Klein, Kristine E. Lee, Xiaoyu Gao, Michael Mauer, Silvia Maeastroni, Maria Luiza Caramori, Ian H. de Boer, Rachel G. Miller, Jingchuan Guo, Andrew P. Boright, David Tregouet, Beata Gyorgy, Janet K. Snell-Bergeon, David M. Maahs, Shelley B. Bull, Angelo J. Canty, Colin N.A. Palmer, Lars Stechemesser, Bernhard Paulweber, Raimund Weitgasser, Jelizaveta Sokolovska, Vita Rovīte, Valdis Pīrāgs, Edita Prakapiene, Lina Radzeviciene, Rasa Verkauskiene, Nicolae Mircea Panduru, Leif C. Groop, Mark I. McCarthy, Harvest F. Gu, Anna Möllsten, Henrik Falhammar, Kerstin Brismar, GENIE Consortium, DCCT/EDIC Research Group, SUMMIT Consortium, Finian Martin, Peter Rossing, Tina Costacou, Gianpaolo Zerbini, Michel Marre, Samy Hadjadj, Amy J. McKnight, Carol Forsblom, Gareth McKay, Catherine Godson, A. Peter Maxwell, Matthias Kretzler, Katalin Susztak, Helen M. Colhoun, Andrzej Krolewski, Andrew D. Paterson, Per-Henrik Groop, Stephen S. Rich, and Joel N. Hirschhorn.
Disclosures: The authors acknowledge the following conflicts of interest: P-H.G. has received investigator-initiated research grants from Eli Lilly and Roche, is an advisory board member for AbbVie, AstraZeneca, Boehringer Ingelheim, Cebix, Eli Lilly, Janssen, Medscape, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi; and has received lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Merck Sharp & Dohme, Medscape, Novo Nordisk and Sanofi. M.I.M. is a Wellcome Investigator and an NIHR Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. He serves on advisory panels for Pfizer, NovoNordisk, and Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; and has received research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier and Takeda. P.R. has received consultancy and/or speaking fees (to his institution) from AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novo Nordisk and Sanofi Aventis and research grants from AstraZeneca and Novo Nordisk, and shares in Novo Nordisk.
The article, entitled “Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen,” will appear online at http://cjasn.asnjournals.org/ on September 19, 2019, doi: 10.1681/ASN.2019030218.
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(JASN) doi: 10.1681/ASN.2019030218