Human Leukocyte Antigens class II (HLA II) gene profile from an admixed population of patients with type 1 diabetes with severe diabetic retinopathy: a nested case-control study in Brazil

Deborah Conte Santos; Luís Cristóvão Porto; Marcela Haas Pizarro; Laura Gomes Nunes de Melo; Dayse A Silva; Romulo Vianna Oliveira; Anna Paula Villela; Luiza Harcar Muniz; Camila Soares; Lucianne Righeti Monteiro Tannus; Karla Rezende Guerra Drummond; André Araújo Pinheiro; Felipe Mallmann; Franz Schubert Lopes Leal; Fernando Korn Malerbi; Paulo Henrique Morales; Marília Brito Gomes

doi:10.1186/s13098-021-00702-y

Human Leukocyte Antigens class II (HLA II) gene profile from an admixed population of patients with type 1 diabetes with severe diabetic retinopathy: a nested case-control study in Brazil

Diabetol Metab Syndr. 2021 Aug 6;13(1):83. doi: 10.1186/s13098-021-00702-y.

Authors

Deborah Conte Santos¹, Luís Cristóvão Porto², Marcela Haas Pizarro³, Laura Gomes Nunes de Melo⁴, Dayse A Silva⁵, Romulo Vianna Oliveira², Anna Paula Villela², Luiza Harcar Muniz³, Camila Soares³, Lucianne Righeti Monteiro Tannus³, Karla Rezende Guerra Drummond⁶, André Araújo Pinheiro⁷, Felipe Mallmann⁸, Franz Schubert Lopes Leal⁹, Fernando Korn Malerbi¹⁰, Paulo Henrique Morales⁶, Marília Brito Gomes³

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. deborahconte@hotmail.com.
² Histocompatibility and Cryopreservation Laboratory (HLA), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil.
³ 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.
⁴ Department of Ophthalmology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ DNA Diagnostic Laboratory (LDD), Rio de Janeiro State University (UERJ), Rio de Janeiro, Rio de Janeiro, Brazil.
⁶ Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.
⁷ Department of Ophthalmology, Regional Hospital of Taguatinga, Brasília, Brazil.
⁸ Department of Ophthalmology, Federal University of Rio Grande Do Sul, Porto Alegre, Brazil.
⁹ Department of Ophthalmology, University of Campinas, Campinas, São Paulo, Brazil.
¹⁰ Department of Endocrinology and Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.

Abstract

Background: Although the well-established role of the HLA genes on the predisposition of type 1 diabetes (T1D), its contribution to the development and progression of diabetic retinopathy is still unclear, especially in admixed populations. We aimed to study the relationship between HLA alleles and severe diabetic retinopathy in a highly admixed population of T1D patients.

Methods: This was a nested case-control study based on a cross-sectional, nationwide survey conducted in Brazil. We included 117 patients with severe diabetic retinopathy and 117 random controls composed of T1D patients without retinopathy, matched for diabetes duration. HLA-class II genes (HLA-DRB1, -DQA1, and -DQB1) were genotyped using the SSO and NGS methods.

Results: Haplotypes HLA-DRB1*04:05 ~ DQA1*03:01 g ~ DQB1*03:02 (OR 1.75, CI 0.97-3.16, p value 0.058) and HLA-DRB1*13:02 ~ DQA1*01:02 ~ DQB1*06:04 (OR 5.18, CI 1.12-23.09, p value 0.019) were more prevalent on the severe DR group but they did not present statistically difference after Bonferroni correction. The most frequent haplotype on both groups was HLA-DRB1*03:01 ~ DQA1*05:01 g ~ DQB1*02:01 (29.6% on severe DR and 33.33% on the control group).

Conclusions: Our study showed no influence of HLA genes on the development of DR. Further longitudinal data is needed to better understand the role of genetic factors on this multifactorial significant microvascular complication.

Keywords: HLA; Human leukocyte antigen; Retinopathy; Type 1 diabetes.

Abstract

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