Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus

de Souza, Amaxsell Thiago Barros; Lucas, Cecília Rodrigues; de Carvalho, Kleyton Thiago Costa; Neta, Antonia Pereira Rosa; Bernardes-Oliveira, Emanuelly; Camargo, Juliana Dantas de Araújo Santos; Luchessi, André Ducati; Cobucci, Ricardo Ney; Crispim, Janaina Cristiana de Oliveira

doi:10.3390/ijerph22030327

Open AccessArticle

Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus

by

Amaxsell Thiago Barros de Souza

¹

,

Cecília Rodrigues Lucas

²,

Kleyton Thiago Costa de Carvalho

³

,

Antonia Pereira Rosa Neta

⁴

,

Emanuelly Bernardes-Oliveira

⁵,

Juliana Dantas de Araújo Santos Camargo

^4,6

,

André Ducati Luchessi

^3,4

,

Ricardo Ney Cobucci

^1,6

and

Janaina Cristiana de Oliveira Crispim

^1,3,5,*

¹

Postgraduate Program in Sciences Applied to Women’s Health, Federal University of Rio Grande do Norte, Natal 59012-310, Brazil

²

Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil

³

Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil

⁴

Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil

⁵

Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil

⁶

Januário Cicco Maternity School, Brazilian Company of Hospital Services (EBSERH), Natal 59012-310, Brazil

^*

Author to whom correspondence should be addressed.

Int. J. Environ. Res. Public Health 2025, 22(3), 327; https://doi.org/10.3390/ijerph22030327

Submission received: 19 December 2024 / Revised: 19 February 2025 / Accepted: 19 February 2025 / Published: 22 February 2025

(This article belongs to the Special Issue New Advances in Diabetes)

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Abstract

Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycemia and insulin resistance, with unclear genetic mechanisms. The specific involvement of proinflammatory cytokines, including IL-17A, and the immuno-tolerogenic HLA-G remains poorly understood in GDM. We aimed to explore the associations of three polymorphisms, IL-17A -197G>A (rs2275913), IL-17RA -947A>G (rs4819554), and HLA-G 14-bp insertion/deletion (indel), with GDM risk in a Brazilian population. We conducted a case-control study (79 GDM cases and 79 controls). Genetic polymorphisms were analyzed using PCR–RFLP, with DNA extracted using the Salting-out procedure. Significant associations were identified between -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms in both codominant and recessive models. The IL-17A rs2275913 AA genotype was associated with a nearly ten-fold increased risk of GDM in both the codominant (p = 0.021, OR 9.89, 95% CI: 1.63–59.92) and recessive models (p = 0.006, OR 9.33, 95% CI: 1.57–55.38). Similarly, the HLA-G 14-bp Ins/Ins genotype was associated with an increased risk in both the codominant (p = 0.026, OR 3.34, 95% CI: 0.98–11.41) and recessive models (p = 0.010, OR 4.20, 95% CI: 1.36–12.96). IL-17RA polymorphism showed no significant associations. The study findings highlight the potential genetic and immune factors associated with GDM, particularly the -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms. Further functional characterization is warranted to uncover the mechanism of genotype–phenotype association.

Keywords: Gestational Diabetes Mellitus; IL-17A polymorphism; IL-17RA polymorphism; HLA-G 14-bp insertion/deletion; genetic association

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MDPI and ACS Style

de Souza, A.T.B.; Lucas, C.R.; de Carvalho, K.T.C.; Neta, A.P.R.; Bernardes-Oliveira, E.; Camargo, J.D.d.A.S.; Luchessi, A.D.; Cobucci, R.N.; Crispim, J.C.d.O. Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus. Int. J. Environ. Res. Public Health 2025, 22, 327. https://doi.org/10.3390/ijerph22030327

AMA Style

de Souza ATB, Lucas CR, de Carvalho KTC, Neta APR, Bernardes-Oliveira E, Camargo JDdAS, Luchessi AD, Cobucci RN, Crispim JCdO. Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus. International Journal of Environmental Research and Public Health. 2025; 22(3):327. https://doi.org/10.3390/ijerph22030327

Chicago/Turabian Style

de Souza, Amaxsell Thiago Barros, Cecília Rodrigues Lucas, Kleyton Thiago Costa de Carvalho, Antonia Pereira Rosa Neta, Emanuelly Bernardes-Oliveira, Juliana Dantas de Araújo Santos Camargo, André Ducati Luchessi, Ricardo Ney Cobucci, and Janaina Cristiana de Oliveira Crispim. 2025. "Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus" International Journal of Environmental Research and Public Health 22, no. 3: 327. https://doi.org/10.3390/ijerph22030327

APA Style

de Souza, A. T. B., Lucas, C. R., de Carvalho, K. T. C., Neta, A. P. R., Bernardes-Oliveira, E., Camargo, J. D. d. A. S., Luchessi, A. D., Cobucci, R. N., & Crispim, J. C. d. O. (2025). Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus. International Journal of Environmental Research and Public Health, 22(3), 327. https://doi.org/10.3390/ijerph22030327

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Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus

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