Zaliunas Balys Remigijus, Gedvilaite-Vaicechauskiene Greta, Kriauciuniene Loresa, Tamasauskas Arimantas, Liutkeviciene Rasa
Medical Faculty, Lithuanian University of Health Sciences, Medical Academy, 44307 Kaunas, Lithuania.
Neuroscience Institute, Lithuanian University of Health Sciences, Medical Academy, 44307 Kaunas, Lithuania.
Cancers (Basel). 2024 Jul 10;16(14):2509. doi: 10.3390/cancers16142509.
The aim of this study was to determine associations of (rs867186), (rs237025), (rs13278372) gene polymorphisms and , , protein levels with clinical and morphological features of pituitary adenomas (PAs).
This case-control study included 459 individuals divided into two groups: a control group ( = 320) and a group of individuals with PAs ( = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for (rs867186), (rs237025), and (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer's recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0".
We found significant differences in (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% ( < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA ( < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold ( < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model ( < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% ( < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% ( < 0.001), and the G allele was less common (13.7% vs. 34.2%, < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold ( = 0.001), and each G allele reduced microadenoma odds by 3.1-fold ( < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model ( < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA ( < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold ( < 0.001), and each G allele reduced odds by 2.2-fold in the additive model ( < 0.001).
The (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors.
本研究旨在确定（rs867186）、（rs237025）、（rs13278372）基因多态性以及TRAF2、TAB2、IKBKB蛋白水平与垂体腺瘤（PAs）临床和形态学特征之间的关联。
本病例对照研究纳入459名个体，分为两组：对照组（n = 320）和垂体腺瘤患者组（n = 139）。采用盐沉淀法和柱法从外周血白细胞中分离DNA。采用实时荧光定量PCR对（rs867186）、（rs237025）和（rs13278372）进行单核苷酸多态性（SNP）基因分型，并根据制造商的建议，使用商业酶联免疫吸附测定（ELISA）试剂盒通过免疫酶分析试验测量TRAF2、TAB2、IKBKB蛋白浓度。使用单克隆抗体（克隆号SP6；Spring Bioscience Corporation）通过免疫组织化学分析确定标记指数Ki-67。使用“IBM SPSS Statistics 29.0”程序进行统计数据分析。
我们发现两组之间（rs867186）基因型（AA、AG、GG）存在显著差异：79.1%、17.3%、3.6% 对比 55.3%、20.9%、23.8%（P < 0.001）。垂体腺瘤组中G等位基因的频率低于对照组（12.2% 对比 34.2%，P < 0.001）。与AA基因型相比，AG和GG基因型使垂体腺瘤发生风险分别降低1.74倍和9.43倍（P < 0.001）。在显性模型中，GG和AG基因型使垂体腺瘤发生风险降低3.07倍，而在隐性模型中，GG基因型使垂体腺瘤发生风险降低8.33倍（P < 0.001）。在加性模型中，每个G等位基因使垂体腺瘤发生风险降低2.49倍（P < 0.001）。与对照组相比，微腺瘤的基因型存在显著差异：81.3%、18.8%、0.0% 对比 55.3%、20.9%、23.8%（P < 0.001），G等位基因频率较低（9.4% 对比 34.2%，P < 0.001）。在大腺瘤中，基因型差异为78%、16.5%、5.5% 对比 55.3%、20.9%、23.8%（P < 0.001），G等位基因较少见（13.7% 对比 34.2%，P < 0.001）。显性模型显示，GG和AG基因型使微腺瘤发生风险降低3.5倍（P = 0.001），每个G等位基因使微腺瘤发生风险降低3.1倍（P < 0.001）。对于大腺瘤，在共显性模型中，GG基因型使发生风险降低6.1倍（P < 0.001），与AA基因型相比，GG和AG基因型联合使发生风险降低2.9倍（P < 0.001）。隐性模型表明，GG基因型使大腺瘤发生风险降低5.3倍（P < 0.001），在加性模型中，每个G等位基因使发生风险降低2.2倍（P < 0.001）。
与AA基因型相比，（rs867186）G等位基因和GG基因型与垂体腺瘤（包括微腺瘤和大腺瘤）发生风险降低显著相关。这些发现表明G等位基因对这些肿瘤的发生具有保护作用。
