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

摘要/Abstract

摘要： 目的分析配对盒基因4(paired box 4, PAX4)变异与妊娠期糖尿病(gestational diabetes mellitus, GDM)发生风险、糖代谢表型、胰岛素治疗需求及围产结局的关联。方法采用病例对照研究,纳入2022年1月至2024年1月山东大学齐鲁医院(青岛)就诊并诊断为GDM孕妇99例(GDM组),同期在青岛市立医院产检的糖耐量正常(normal glucose tolerance, NGT)孕妇100例(NGT组)。采用高通量二代测序法对13个青少年发病的成人型糖尿病(maturity-onset diabetes of the young, MODY)相关基因进行检测。比较两组PAX4变异分布,并采用logistic回归分析PAX4变异与GDM发生风险的关联。在GDM中,采用线性回归分析PAX4变异与血糖和胰岛功能指标的关联,采用logistic回归分析与胰岛素治疗需求和剖宫产的关联,采用Firth惩罚logistic回归分析与巨大儿、低出生体质量和早产的关联。结果 GDM组PAX4变异检出率高于NGT组(27.27% vs. 14.00%,P=0.021)。调整年龄、胎次和口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)检测时的体质量后,PAX4变异可能与GDM发生风险增加相关(OR=2.499,95%CI:1.102~5.670,P=0.028)。在GDM组中,调整年龄、孕前体质量指数和糖尿病家族史后,PAX4变异可能与空腹血糖升高相关(β=0.074,95%CI:0.010~0.138,P=0.023),与C肽(β=-0.670,95%CI:-1.225~-0.115,P=0.019)、胰岛素(β=-0.282,95%CI:-0.498~-0.065,P=0.011)、HOMA-β降低(β=-0.249,95%CI:-0.472~-0.026,P=0.029)相关,可能与胰岛素治疗需求增加相关(OR=3.797,95%CI:1.446~9.972,P=0.007),还可能与巨大儿发生风险升高相关(OR=4.182,95%CI:1.211~15.561,P=0.023)。敏感性分析与主分析结果基本一致。结论 PAX4变异可能与GDM易感性增加和β细胞分泌功能受损相关,可为GDM遗传学分层和个体化管理提供初步线索。

关键词: 妊娠期糖尿病, 配对盒基因4, 基因检测, β细胞功能, 围产结局

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

中图分类号:

R587.1

马小莉,林华,孟丽莹,左丹,刘诗群,张有涛,刘元涛,孙靖,张玉超. 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[J]. 山东大学学报 (医学版), 2026, 64(8): 79-88.

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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