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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

Amaxsell Thiago Barros de Souza, 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 ()
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Amaxsell Thiago Barros de Souza: Postgraduate Program in Sciences Applied to Women’s Health, Federal University of Rio Grande do Norte, Natal 59012-310, Brazil
Cecília Rodrigues Lucas: Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
Kleyton Thiago Costa de Carvalho: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
Antonia Pereira Rosa Neta: Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
Emanuelly Bernardes-Oliveira: Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
Juliana Dantas de Araújo Santos Camargo: Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
André Ducati Luchessi: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil
Ricardo Ney Cobucci: Postgraduate Program in Sciences Applied to Women’s Health, Federal University of Rio Grande do Norte, Natal 59012-310, Brazil
Janaina Cristiana de Oliveira Crispim: Postgraduate Program in Sciences Applied to Women’s Health, Federal University of Rio Grande do Norte, Natal 59012-310, Brazil

IJERPH, 2025, vol. 22, issue 3, 1-15

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 (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2025
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