配对盒基因4变异与妊娠期糖尿病发生风险、β细胞功能及围产结局的关联性

doi:10.6040/j.issn.1671-7554.0.2026.0496

Abstract

Abstract: Objective To analyze the association between paired box 4(PAX4)variants and the risk of gestational diabetes mellitus(GDM), glucose metabolic phenotype, insulin treatment requirements, and perinatal outcomes. Methods A case-control study was conducted, including 99 pregnant women with GDM who were treated at Qilu Hospital of Shandong University(Qingdao)from January 2022 to January 2024 and 100 pregnant women with normal glucose tolerance(NGT)who underwent antenatal care at Qingdao Municipal Hospital during the same period. Targeted high-throughput next-generation sequencing was performed to detect 13 genes related to maturity-onset diabetes of the young(MODY). The distribution of PAX4 variants was compared between the two groups. Logistic regression was used to assess the association between PAX4 variants and the risk of GDM. Among women with GDM, linear regression was used to evaluate the associations of PAX4 variants with glycemic and pancreatic islet function indices; logistic regression was used to analyze their associations with insulin therapy requirement and cesarean delivery; Firth penalized logistic regression was used to examine their associations with macrosomia, low birth weight, and preterm birth. Results The detection rate of PAX4 variants was higher in the GDM group than in the NGT group(27.27% vs. 14.00%, P=0.021). After adjustment for age, parity, and body weight at the time of the oral glucose tolerance test(OGTT), PAX4 variants might be associated with an increased risk of GDM(OR=2.499, 95%CI: 1.102-5.670, P=0.028). Among women with GDM, after adjustment for age, pre-pregnancy BMI, and family history of diabetes, PAX4 variants might be associated with higher fasting plasma glucose(β=0.074, 95%CI: 0.010-0.138, P=0.023), lower C-peptide(β=-0.670, 95%CI: -1.225 to -0.115, P=0.019), lower fasting insulin(β=-0.282, 95%CI: -0.498 to -0.065, P=0.011), and lower HOMA-β(β=-0.249, 95%CI: -0.472 to -0.026, P=0.029). PAX4 variants might be associated with an increased requirement for insulin therapy(OR=3.797, 95%CI: 1.446-9.972, P=0.007), and might also be associated with a higher risk of macrosomia(OR=4.182, 95%CI: 1.211-15.561, P=0.023). Sensitivity analyses yielded results generally consistent with those of the primary analysis. Conclusion PAX4 variants may be associated with increased susceptibility to GDM and impaired β-cell secretory function, potentially providing preliminary clues for genetic stratification and individualized management of GDM.

Key words: Gestational diabetes mellitus, Paired box 4, Genetic testing, β-cell function, Perinatal outcomes

CLC Number:

R587.1

MA Xiaoli, LIN Hua, MENG Liying, ZUO Dan, LIU Shiqun, ZHANG Youtao, LIU Yuantao, SUN Jing, ZHANG Yuchao. Association of paired box 4 variants with risk of gestational diabetes mellitus, β-cell function, and perinatal outcomes[J].Journal of Shandong University (Health Sciences), 2026, 64(8): 79-88.

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Association of paired box 4 variants with risk of gestational diabetes mellitus, β-cell function, and perinatal outcomes

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