Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China; Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China.
J Proteomics. 2024 Sep 15;307:105268. doi: 10.1016/j.jprot.2024.105268. Epub 2024 Aug 2.
This study aimed to explore associations of serum cluster of differentiation 44 (CD44) levels and its genetic variants in early pregnancy with gestational diabetes mellitus (GDM). We conducted a 1:1 case-control study (n = 414) nested in a prospective cohort of 22,302 pregnant women recruited from 2010 to 2012 in Tianjin, China. Blood samples were collected at the first antenatal care visit (at a median of 10 gestational week). Binary conditional logistic regressions were performed to examine associations of serum CD44 levels and its genetic variants with increased risk of GDM. In this study, we found that serum CD44 levels in early pregnancy was associated with GDM risk in a U-shaped manner. High serum CD44 levels and its genetic risk score in early pregnancy were associated with markedly increased risk of GDM after adjustment for traditional confounders (OR: 1.95, 95%CI: 1.12-3.40 & 1.95, 1.05-3.61). Furthermore, after adjustment for serum CD44 levels, the OR of CD44 genetic risk score for GDM was slightly attenuated but not significant (1.84, 0.98-3.48). In conclusion, serum CD44 levels and its genetic variants in early pregnancy were associated with GDM risk in Chinese pregnant women, with the effect of CD44 genetic variants being accounted for by serum CD44. SIGNIFICANCE: Recent studies suggested that pregnant women with GDM may have abnormal levels of CD44 and abnormal expression of CD44 gene, but it is uncertain whether abnormal CD44 plays a causal role in occurrence of GDM. Specifically, it remains unknown whether serum CD44 levels in early pregnancy and its genetic variants can predict the later occurrence of GDM. In this study, we found that high serum CD44 levels in early pregnancy and its genetic variants were associated with markedly increased risk of GDM in Chinese pregnant women, with the effect of CD44 genetic variants being largely accounted for by serum CD44 levels. Our study is the first reporting that serum CD44 levels and its genetic variants were associated with markedly increased risk of GDM. These multi-omics risk markers may be useful for identification of women at high risk of GDM in early pregnancy. Our findings also provide new insights into the disease mechanisms.
本研究旨在探讨妊娠早期血清 CD44 水平及其遗传变异与妊娠期糖尿病（GDM）的关联。我们进行了一项 1:1 的病例对照研究（n=414），嵌套于 2010 年至 2012 年在中国天津招募的 22302 名孕妇前瞻性队列中。在第一次产前检查时采集血样（中位数为 10 孕周）。采用二元条件逻辑回归分析妊娠早期血清 CD44 水平及其遗传变异与 GDM 风险增加的关系。在这项研究中，我们发现妊娠早期血清 CD44 水平与 GDM 风险呈 U 型关联。在调整传统混杂因素后，高血清 CD44 水平和妊娠早期 CD44 遗传风险评分与 GDM 的发生风险显著增加相关（OR：1.95，95%CI：1.12-3.40 和 1.95，1.05-3.61）。此外，在调整血清 CD44 水平后，CD44 遗传风险评分对 GDM 的 OR 略有减弱但无统计学意义（1.84，0.98-3.48）。总之，中国孕妇妊娠早期血清 CD44 水平及其遗传变异与 GDM 风险相关，CD44 遗传变异的作用部分由血清 CD44 水平解释。意义：最近的研究表明，患有 GDM 的孕妇可能存在 CD44 水平异常和 CD44 基因异常表达，但尚不确定异常 CD44 是否在 GDM 的发生中起因果作用。具体来说，妊娠早期血清 CD44 水平及其遗传变异是否能预测 GDM 的发生尚不清楚。在这项研究中，我们发现妊娠早期高血清 CD44 水平及其遗传变异与中国孕妇 GDM 的发生风险显著增加相关，CD44 遗传变异的作用主要由血清 CD44 水平解释。本研究首次报道了妊娠早期血清 CD44 水平及其遗传变异与 GDM 发生风险显著增加相关。这些多组学风险标志物可能有助于在妊娠早期识别 GDM 高危妇女。我们的研究结果还为疾病机制提供了新的见解。
