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Published in: Acta Diabetologica 8/2020

01-08-2020 | Diabetic Retinopathy | Original Article

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

Authors: Deborah Conte Santos, Laura Gomes Nunes de Melo, Marcela Haas Pizarro, Bianca S. V. Barros, Carlos Antonio Negrato, Luís Cristóvão Porto, Dayse A. Silva, Karla Rezende Guerra Drummond, Luiza Harcar Muniz, Tessa Cerqueria Lemos Mattos, André Araújo Pinheiro, Felipe Mallmann, Franz Schubert Lopes Leal, Fernando Korn Malerbi, Paulo Henrique Morales, Marília Brito Gomes

Published in: Acta Diabetologica | Issue 8/2020

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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.
Literature
1.
go back to reference Gomes MB, Negrato CA (2015) Retirement due to disabilities in patients with type 1 diabetes a nationwide multicenter survey in Brazil. BMC Public Health 15(1):486PubMedPubMedCentral Gomes MB, Negrato CA (2015) Retirement due to disabilities in patients with type 1 diabetes a nationwide multicenter survey in Brazil. BMC Public Health 15(1):486PubMedPubMedCentral
2.
go back to reference Leasher JL, Bourne RRA, Flaxman SR et al (2016) Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care 39(9):1643–1649PubMed Leasher JL, Bourne RRA, Flaxman SR et al (2016) Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care 39(9):1643–1649PubMed
3.
go back to reference Nathan DM (2014) The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care 37(1):9–16PubMed Nathan DM (2014) The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care 37(1):9–16PubMed
4.
go back to reference Hassan K, Loar R, Anderson BJ, Heptulla RA (2006) The role of socioeconomic status, depression, quality of life, and glycemic control in type 1 diabetes mellitus. J Pediatr 149(4):526–531PubMed Hassan K, Loar R, Anderson BJ, Heptulla RA (2006) The role of socioeconomic status, depression, quality of life, and glycemic control in type 1 diabetes mellitus. J Pediatr 149(4):526–531PubMed
5.
go back to reference Willi SM, Miller KM, Di Meglio LA et al (2015) Racial-ethnic disparities in management and outcomes among children with type 1 diabetes. Pediatrics 135:424–434PubMedPubMedCentral Willi SM, Miller KM, Di Meglio LA et al (2015) Racial-ethnic disparities in management and outcomes among children with type 1 diabetes. Pediatrics 135:424–434PubMedPubMedCentral
6.
go back to reference Liu Y, Yang J, Tao L et al (2017) Risk factors of diabetic retinopathy and sight-threatening diabetic retinopathy: a cross-sectional study of 13 473 patients with type 2 diabetes mellitus in mainland China. BMJ Open 7(9):e016280PubMedPubMedCentral Liu Y, Yang J, Tao L et al (2017) Risk factors of diabetic retinopathy and sight-threatening diabetic retinopathy: a cross-sectional study of 13 473 patients with type 2 diabetes mellitus in mainland China. BMJ Open 7(9):e016280PubMedPubMedCentral
7.
go back to reference Sasongko MB, Widyaputri F, Agni AN et al (2017) Prevalence of diabetic retinopathy and blindness in Indonesian adults with type 2 diabetes. Am J Ophthalmol 181:79–87PubMed Sasongko MB, Widyaputri F, Agni AN et al (2017) Prevalence of diabetic retinopathy and blindness in Indonesian adults with type 2 diabetes. Am J Ophthalmol 181:79–87PubMed
8.
go back to reference Raymond NT, Varadhan L, Reynold DR et al (2009) Higher prevalence of retinopathy in diabetic patients of South Asian ethnicity compared with white Europeans in the community: a cross-sectional study. Diabetes Care 32(3):410–415PubMedPubMedCentral Raymond NT, Varadhan L, Reynold DR et al (2009) Higher prevalence of retinopathy in diabetic patients of South Asian ethnicity compared with white Europeans in the community: a cross-sectional study. Diabetes Care 32(3):410–415PubMedPubMedCentral
9.
go back to reference Sivaprasad S, Gupta B, Gulliford MC et al (2012) Ethnic variations in the prevalence of diabetic retinopathy in people with diabetes attending screening in the United Kingdom (DRIVE UK). PLoS ONE 7(3):e32182PubMedPubMedCentral Sivaprasad S, Gupta B, Gulliford MC et al (2012) Ethnic variations in the prevalence of diabetic retinopathy in people with diabetes attending screening in the United Kingdom (DRIVE UK). PLoS ONE 7(3):e32182PubMedPubMedCentral
10.
go back to reference Gao X, Gauderman WJ, Marjoram P et al (2014) Native American ancestry is associated with severe diabetic retinopathy in Latinos. Invest Ophthalmol Vis Sci 55(9):6041–6045PubMedPubMedCentral Gao X, Gauderman WJ, Marjoram P et al (2014) Native American ancestry is associated with severe diabetic retinopathy in Latinos. Invest Ophthalmol Vis Sci 55(9):6041–6045PubMedPubMedCentral
11.
go back to reference Tandon A, Chen CJ, Penman A et al (2015) African Ancestry analysis and admixture genetic mapping for proliferative diabetic retinopathy in African Americans. Invest Ophthalmol Vis Sci 56(6):3999–4005PubMedPubMedCentral Tandon A, Chen CJ, Penman A et al (2015) African Ancestry analysis and admixture genetic mapping for proliferative diabetic retinopathy in African Americans. Invest Ophthalmol Vis Sci 56(6):3999–4005PubMedPubMedCentral
12.
go back to reference Patterson N, Hattangadi N, Lane B et al (2004) Methods for high-density admixture mapping of disease genes. Am J Hum Genet 74(5):979–1000PubMedPubMedCentral Patterson N, Hattangadi N, Lane B et al (2004) Methods for high-density admixture mapping of disease genes. Am J Hum Genet 74(5):979–1000PubMedPubMedCentral
13.
go back to reference Wong TY, Klein R, Islam FMA et al (2006) Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol 141(3):446–455PubMedPubMedCentral Wong TY, Klein R, Islam FMA et al (2006) Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol 141(3):446–455PubMedPubMedCentral
14.
go back to reference Tan GS, Gan A, Sabanayagam C et al (2018) Ethnic differences in the prevalence and risk factors of diabetic retinopathy: the Singapore epidemiology of eye diseases study. Ophthalmology 125(4):529–536PubMed Tan GS, Gan A, Sabanayagam C et al (2018) Ethnic differences in the prevalence and risk factors of diabetic retinopathy: the Singapore epidemiology of eye diseases study. Ophthalmology 125(4):529–536PubMed
16.
go back to reference Banda Y, Kvale MN, Hoffmann TJ et al (2015) Characterizing race/ethnicity and genetic ancestry for 100,000 subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetics 200(4):1285–1295PubMedPubMedCentral Banda Y, Kvale MN, Hoffmann TJ et al (2015) Characterizing race/ethnicity and genetic ancestry for 100,000 subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetics 200(4):1285–1295PubMedPubMedCentral
17.
go back to reference Cardena MMSG, Ribeiro-dos-Santos Â, Santos S, Mansur AJ, Pereira AC, Fridman C (2013) Assessment of the relationship between self-declared ethnicity, mitochondrial haplogroups and genomic ancestry in Brazilian individuals. PLoS ONE 8(4):e62005PubMedPubMedCentral Cardena MMSG, Ribeiro-dos-Santos Â, Santos S, Mansur AJ, Pereira AC, Fridman C (2013) Assessment of the relationship between self-declared ethnicity, mitochondrial haplogroups and genomic ancestry in Brazilian individuals. PLoS ONE 8(4):e62005PubMedPubMedCentral
18.
go back to reference Gomes MB, Rodacki M, Pavin EJ et al (2017) The impact of ethnicity, educational and economic status on the prescription of insulin therapeutic regimens and on glycemic control in patients with type 1 diabetes. A nationwide study in Brazil. Diabetes Res Clin Pract 134:44–52PubMed Gomes MB, Rodacki M, Pavin EJ et al (2017) The impact of ethnicity, educational and economic status on the prescription of insulin therapeutic regimens and on glycemic control in patients with type 1 diabetes. A nationwide study in Brazil. Diabetes Res Clin Pract 134:44–52PubMed
19.
go back to reference Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedPubMedCentral Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedPubMedCentral
21.
go back to reference Schellini SA, Carvalho GM, Rendeiro FS, Padovani CR, Hirai FE (2014) Prevalence of diabetes and diabetic retinopathy in a Brazilian population. Ophthalmic Epidemiol 21(1):33–38PubMed Schellini SA, Carvalho GM, Rendeiro FS, Padovani CR, Hirai FE (2014) Prevalence of diabetes and diabetic retinopathy in a Brazilian population. Ophthalmic Epidemiol 21(1):33–38PubMed
23.
go back to reference Wilkinson CP, Ferris FL, Klein RE et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682PubMed Wilkinson CP, Ferris FL, Klein RE et al (2003) Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110(9):1677–1682PubMed
24.
go back to reference Pereira R, Phillips C, Pinto N et al (2012) Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing. PLoS ONE 7(1):e29684PubMedPubMedCentral Pereira R, Phillips C, Pinto N et al (2012) Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing. PLoS ONE 7(1):e29684PubMedPubMedCentral
25.
go back to reference Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959PubMedPubMedCentral Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959PubMedPubMedCentral
26.
go back to reference Posth C, Nakatsuka N, Lazaridis I et al (2018) Reconstructing the deep population history of Central and South America. Cell 175(5):1185–1197PubMedPubMedCentral Posth C, Nakatsuka N, Lazaridis I et al (2018) Reconstructing the deep population history of Central and South America. Cell 175(5):1185–1197PubMedPubMedCentral
27.
go back to reference Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J (2012) Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol 57(4):347–370PubMed Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J (2012) Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol 57(4):347–370PubMed
28.
go back to reference Lee ET, Lu M, Bennett PH, Keen H, Group WHOMS (2001) Vascular disease in younger-onset diabetes: comparison of European, Asian and American Indian cohorts of the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 44(2):S78PubMed Lee ET, Lu M, Bennett PH, Keen H, Group WHOMS (2001) Vascular disease in younger-onset diabetes: comparison of European, Asian and American Indian cohorts of the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 44(2):S78PubMed
29.
go back to reference Emanuele N, Moritz T, Klein R et al (2009) Ethnicity, race, and clinically significant macular edema in the Veterans Affairs Diabetes Trial (VADT). Diabetes Res Clin Pract 86(2):104–110PubMed Emanuele N, Moritz T, Klein R et al (2009) Ethnicity, race, and clinically significant macular edema in the Veterans Affairs Diabetes Trial (VADT). Diabetes Res Clin Pract 86(2):104–110PubMed
30.
go back to reference Motala AA, Pirie FJ, Gouws E, Amod A, Omar MAK (2001) Microvascular complications in South African patients with long duration diabetes mellitus. S Afr Med J 91(11):987–992PubMed Motala AA, Pirie FJ, Gouws E, Amod A, Omar MAK (2001) Microvascular complications in South African patients with long duration diabetes mellitus. S Afr Med J 91(11):987–992PubMed
31.
go back to reference Klein R, Rucker CS, Santiago JV (1994) Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus. Arch Intern Med 154:2597–2602PubMed Klein R, Rucker CS, Santiago JV (1994) Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus. Arch Intern Med 154:2597–2602PubMed
32.
go back to reference Bachmann MO, Eachus J, Hopper CD et al (2003) Socio-economic inequalities in diabetes complications, control, attitudes and health service use: a cross-sectional study. Diabet Med 20(11):921–929PubMed Bachmann MO, Eachus J, Hopper CD et al (2003) Socio-economic inequalities in diabetes complications, control, attitudes and health service use: a cross-sectional study. Diabet Med 20(11):921–929PubMed
33.
go back to reference Benoit SR, Swenor B, Geiss LS, Gregg EW, Saaddine JB (2019) Eye care utilization among insured people with diabetes in the US, 2010–2014. Diabetes Care 42(3):427–433PubMed Benoit SR, Swenor B, Geiss LS, Gregg EW, Saaddine JB (2019) Eye care utilization among insured people with diabetes in the US, 2010–2014. Diabetes Care 42(3):427–433PubMed
34.
go back to reference Do DV, Wang X, Vedula SS et al (2015) Blood pressure control for diabetic retinopathy. Sao Paulo Med J 133(3):278–279PubMed Do DV, Wang X, Vedula SS et al (2015) Blood pressure control for diabetic retinopathy. Sao Paulo Med J 133(3):278–279PubMed
35.
go back to reference Kola LD, Sumaili EK, Krzesinski JM (2009) How to treat hypertension in blacks: review of the evidence. Acta Clin Belg 64(6):466–476PubMed Kola LD, Sumaili EK, Krzesinski JM (2009) How to treat hypertension in blacks: review of the evidence. Acta Clin Belg 64(6):466–476PubMed
36.
go back to reference Marden JR, Walter S, Kaufman JS, Glymour MM (2016) African ancestry, social factors, and hypertension among non-Hispanic blacks in the health and retirement study. Biodemogr Soc Biol 62(1):19–35 Marden JR, Walter S, Kaufman JS, Glymour MM (2016) African ancestry, social factors, and hypertension among non-Hispanic blacks in the health and retirement study. Biodemogr Soc Biol 62(1):19–35
37.
go back to reference De Boer IH, Rue TC, Cleary PA et al (2011) Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Arch Intern Med 171(5):412–420PubMedPubMedCentral De Boer IH, Rue TC, Cleary PA et al (2011) Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria: an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Arch Intern Med 171(5):412–420PubMedPubMedCentral
38.
go back to reference Parving H-H, Hommel E, Mathiesen E et al (1988) Prevalence of microalbuminuria, arterial hypertension, retinopathy, and neuropathy in patients with insulin dependent diabetes. Br Med J Clin Res Ed 296(6616):156PubMedPubMedCentral Parving H-H, Hommel E, Mathiesen E et al (1988) Prevalence of microalbuminuria, arterial hypertension, retinopathy, and neuropathy in patients with insulin dependent diabetes. Br Med J Clin Res Ed 296(6616):156PubMedPubMedCentral
39.
go back to reference Udler MS, Nadkarni GN, Belbin G et al (2015) Effect of genetic African ancestry on eGFR and kidney disease. J Am Soc Nephrol 26(7):1682–1692PubMed Udler MS, Nadkarni GN, Belbin G et al (2015) Effect of genetic African ancestry on eGFR and kidney disease. J Am Soc Nephrol 26(7):1682–1692PubMed
40.
go back to reference Malerbi FK, Morales PH, Farah ME et al (2015) Comparison between binocular indirect ophthalmoscopy and digital retinography for diabetic retinopathy screening: the multicenter Brazilian Type 1 Diabetes Study. Diabetol Metab Syndr 7(1):116PubMedPubMedCentral Malerbi FK, Morales PH, Farah ME et al (2015) Comparison between binocular indirect ophthalmoscopy and digital retinography for diabetic retinopathy screening: the multicenter Brazilian Type 1 Diabetes Study. Diabetol Metab Syndr 7(1):116PubMedPubMedCentral
Metadata
Title
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
Authors
Deborah Conte Santos
Laura Gomes Nunes de Melo
Marcela Haas Pizarro
Bianca S. V. Barros
Carlos Antonio Negrato
Luís Cristóvão Porto
Dayse A. Silva
Karla Rezende Guerra Drummond
Luiza Harcar Muniz
Tessa Cerqueria Lemos Mattos
André Araújo Pinheiro
Felipe Mallmann
Franz Schubert Lopes Leal
Fernando Korn Malerbi
Paulo Henrique Morales
Marília Brito Gomes
Publication date
01-08-2020
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 8/2020
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-020-01498-5

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