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Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case–control study in Brazil

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Abstract

Aims

The influence of genetic factors on the development and progression of diabetic retinopathy is still unclear. Previous studies showed controversial results. We aimed to characterize the relationship between genomic ancestry and self-reported color/race with severe diabetic retinopathy in patients with type 1 diabetes belonging to a highly admixed population.

Methods

This study was a nested case–control based on data collected from a large cross-sectional, nationwide survey conducted in clinics from all five geographic regions of Brazil. For the present study, we included 414 individuals. Cases (n = 176) were considered if they had severe non-proliferative or proliferative diabetic retinopathy, and controls (n = 238) were type 1 diabetes patients without retinopathy, matched for diabetes duration by a range of 5 years. Indirect ophthalmoscopy was performed, and individual genomic ancestry was inferred using a panel of 46 ancestry informative markers.

Results

The backward stepwise logistic regression analysis showed that African genomic ancestry (OR 3.9, p = 0.045), HbA1c (OR 1.24, p = 0.001), glomerular filtration rate (OR 0.98, p < 0.001) and hypertension (OR 2.52, p < 0.001) were associated with severe diabetic retinopathy after adjusting for clinical and demographic data. Self-reported color/race was not statistically associated with diabetic retinopathy.

Conclusions

Genomic ancestry, as well as clinical variables such as hypertension, impaired glomerular filtration rate and poor diabetes control (HbA1c), was important risk factor for the development of severe diabetic retinopathy. Further studies are needed, especially in highly admixed populations, to better understand the role of genomic ancestry and possible genes that might be associated with the development and/or progression of diabetic retinopathy.

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Acknowledgements

We would like to aknowledge the Brazilian Type 1 Diabetes Study Group BrazDiab1SG for data collection: Executive steering committee: Marilia Brito Gomes (chair), Carlos Antonio Negrato. Principal investigators are indicated by an asterisk. Department of Internal Medicine, Diabetes Unit, State University of Rio de Janeiro, Brazil: Marilia Brito Gomes* (mariliabgomes@gmail.com). Department of Internal Medicine, Diabetes Unit, State University of Rio de Janeiro, Brazil: Roberta Cobas (robertacobas@gmail.com) Lucianne Righeti Monteiro Tannus (luciannetannus@ig.com.br). Federal University Hospital of Rio de Janeiro: Melanie Rodacki*, M.D. (mrodacki2001@yahoo.com.br); Lenita Zajdenverg, M.D. (lenitazaj@gmail.com) Joana Rodrigues Dantas, M.D. (joanardantasp@ig.com.br). Diabetes Unit, University Hospital of São Paulo, São Paulo: Maria Lúcia Cardillo Corrêa-Giannella*, M.D. (malugia@lim25fm.usp.br); Sharon Nina Admoni, M.D. (sharonadmoni@gmail.com); Daniele Pereira dos Santos, M.D. (dps.daniele@hotmail.com). Bauru’s Diabetics Association, Bauru, São Paulo: Carlos Antonio Negrato*, M.D. (carlosnegrato@uol.com.br); Maria de Fatima Guedes, M.D. (tatiguedeses@hotmail.com).Diabetes Unit, Federal University of São Paulo State, São Paulo: Sergio Atala Dib*, M.D. (sergio.dib@unifesp.br); Celso Ferreira de Camargo Sallum Filho, M.D. (celsosallum@superig.com.br). Diabetes Unit, University of Campinas, São Paulo: Elisabeth João Pavin*, M.D. (ejpavin@fcm.unicamp.br); Caroline Takano, M.D. (caroline.takano@gmail.com).Clinical Hospital of the Federal University of Paraná: Rosângela Roginski Rea*, M.D. (rosangelarea@uol.com.br); Nicole Balster Romanzini, M.D. (nikbr@hotmail.com). Clinical Hospital of Porto Alegre, Rio Grande do Sul: Mirela Azevedo*, M.D. (mirelajobimazevedo@gmail.com); Luis Henrique Canani, M.D. (luishenriquecanani@gmail.com). Regional Hospital of Taguatinga, Brasília: Hermelinda Cordeiro Pedrosa*, M.D. (pedrosa.hc@globo.com); Monica Tolentino (monicatolentino@uol.com.br); Cejana Hamu Aguiar, M.D. Diabetes and Endocrinology Center of Bahia: Reine Marie Chaves Fonseca*, M.D. (reinemar@terra.com.br); Ludmila Chaves Fonseca M.D., Raffaele Kasprowicz, M.D. (raffaellebarros@hotmail.com). Diabetes and Hypertension Center of Ceará : Adriana Costa e Forti*, M.D. (adrianaforti@uol.com.br); Angela Delmira Nunes Mendes, M.D. (angeladelmira@terra.com.br). Federal University of Ceará: Renan Montenegro Junior*, M. D. (renanjr@ufc.br); Virgínia Oliveira Fernandes, M.D. (virginiafernande@hotmail.com). Federal University Hospital of Pará: João Soares Felício*, M.D. (felicio.bel@terra.com.br); Flavia Marques Santos, M.D. (drafms@bol.com.br).

Funding

This study was funded by FAPERJ—Fundação do Amparo à Pesquisa do Estado do Rio de Janeiro (Grant No. E-26/110.170/2013) and CNPq—Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil (Grant No. 563753/2010-2).

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Authors and Affiliations

  1. Department of Internal Medicine, Diabetes Unit, Rio de Janeiro State University (UERJ), Boulevard 28 de Setembro, 77- 3º andar - Vila Isabel, Rio de Janeiro, Rio de Janeiro, CEP 20551-030, Brazil

    Deborah Conte Santos, Marcela Haas Pizarro, Bianca S. V. Barros, Luiza Harcar Muniz & Marília Brito Gomes

  2. Department of Ophthalmology, State University of Rio de Janeiro, Rio de Janeiro, Brazil

    Laura Gomes Nunes de Melo

  3. University of São Paulo, Bauru, Brazil

    Carlos Antonio Negrato

  4. Histocompatibility and Cryopreservation Laboratory (HLA), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil

    Luís Cristóvão Porto

  5. DNA Diagnostic Laboratory (LDD), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil

    Dayse A. Silva

  6. Department of Ophthalmology, Federal Hospital of the Servers of Rio de Janeiro, Rio de Janeiro, Brazil

    Karla Rezende Guerra Drummond

  7. Department of Ophthalmology, Center of Endocrinology and Diabetes of the State of Bahia, Salvador, Brazil

    Tessa Cerqueria Lemos Mattos

  8. Department of Ophthalmology, Regional Hospital of Taguatinga, Brasília, Brazil

    André Araújo Pinheiro

  9. Department of Ophthalmology, Federal University of Rio Grande Do Sul, Porto Alegre, Brazil

    Felipe Mallmann

  10. Department of Ophthalmology, University of Campinas, Campinas, São Paulo, Brazil

    Franz Schubert Lopes Leal

  11. Department of Endocrinology and Ophthalmology, Federal University of São Paulo, São Paulo, Brazil

    Fernando Korn Malerbi

  12. Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil

    Paulo Henrique Morales

Authors
  1. Deborah Conte Santos
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  2. Laura Gomes Nunes de Melo
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  3. Marcela Haas Pizarro
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  4. Bianca S. V. Barros
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  5. Carlos Antonio Negrato
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  6. Luís Cristóvão Porto
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  7. Dayse A. Silva
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  8. Karla Rezende Guerra Drummond
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  9. Luiza Harcar Muniz
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  10. Tessa Cerqueria Lemos Mattos
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  12. Felipe Mallmann
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  13. Franz Schubert Lopes Leal
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  14. Fernando Korn Malerbi
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  15. Paulo Henrique Morales
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  16. Marília Brito Gomes
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Corresponding author

Correspondence to Deborah Conte Santos.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

This study was approved by the Ethics Committee of Pedro Ernesto University Hospital (Rio de Janeiro State University) and by the local ethics committee of each center.

Informed consent

Written informed consent was obtained from all participants or their parents.

Additional information

This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.

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Santos, D.C., de Melo, L.G.N., Pizarro, M.H. et al. Genomic ancestry as a risk factor for diabetic retinopathy in patients with type 1 diabetes from an admixed population: a nested case–control study in Brazil. Acta Diabetol 57, 937–945 (2020). https://doi.org/10.1007/s00592-020-01498-5

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