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白细胞介素-17A纯合子AA基因型及HLA-G 3'非翻译区14碱基插入多态性与妊娠期糖尿病风险增加相关。

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.

作者信息

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

机构信息

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

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

出版信息

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

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, -197G>A (rs2275913), -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 rs2275913 AA genotype was associated with a nearly ten-fold increased risk of GDM in both the codominant ( = 0.021, OR 9.89, 95% CI: 1.63-59.92) and recessive models ( = 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 ( = 0.026, OR 3.34, 95% CI: 0.98-11.41) and recessive models ( = 0.010, OR 4.20, 95% CI: 1.36-12.96). 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.

摘要

妊娠期糖尿病(GDM)是一种常见的妊娠并发症,其特征为高血糖和胰岛素抵抗,遗传机制尚不清楚。包括白细胞介素-17A(IL-17A)在内的促炎细胞因子以及免疫耐受原性的人类白细胞抗原G(HLA-G)在GDM中的具体作用仍知之甚少。我们旨在探讨三种多态性,即-197G>A(rs2275913)、-947A>G(rs4819554)和HLA-G 14碱基插入/缺失(indel)与巴西人群GDM风险的关联。我们进行了一项病例对照研究(79例GDM病例和79例对照)。使用盐析法提取DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析基因多态性。在共显性和隐性模型中,均发现-197G>A rs2275913与HLA-G 14碱基indel多态性之间存在显著关联。rs2275913 AA基因型在共显性模型(P = 0.021,比值比[OR] 9.89,95%置信区间[CI]:1.63 - 59.92)和隐性模型(P = 0.006,OR 9.33,95% CI:1.57 - 55.38)中均与GDM风险增加近10倍相关。同样,HLA-G 14碱基Ins/Ins基因型在共显性模型(P = 0.026,OR 3.34,95% CI:0.98 - 11.41)和隐性模型(P = 0.010,OR 4.20,95% CI:1.36 - 12.96)中均与风险增加相关。-947A>G多态性未显示出显著关联。研究结果突出了与GDM相关的潜在遗传和免疫因素,特别是-197G>A rs2275913和HLA-G 14碱基indel多态性。有必要进一步进行功能表征以揭示基因型-表型关联的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6443/11941881/3481d929c18d/ijerph-22-00327-g001.jpg

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