Aim: The aim of this study was to determine associations ofTRAF2(rs867186),TAB2(rs237025),IKBKB(rs13278372) gene polymorphisms andTRAF2,TAB2,IKBKBprotein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals divided into two groups: a control group (n= 320) and a group of individuals with PAs (n= 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used forTRAF2(rs867186),TAB2(rs237025), andIKBKB(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". Results: We found significant differences inTRAF2(rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p< 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%,p< 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p< 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 (p< 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p< 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p< 0.001), with the G allele being less frequent (9.4% vs. 34.2%,p< 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p< 0.001), and the G allele was less common (13.7% vs. 34.2%,p< 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p= 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p< 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p< 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p< 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p< 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p< 0.001). Conclusions: TheTRAF2(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.
目的：本研究旨在探讨TRAF2(rs867186)、TAB2(rs237025)、IKBKB(rs13278372)基因多态性及TRAF2、TAB2、IKBKB蛋白水平与垂体腺瘤（PAs）临床及形态学特征的相关性。方法：本病例对照研究共纳入459名受试者，分为两组：对照组（n=320）和垂体腺瘤组（n=139）。采用盐沉淀法和柱法分离外周血白细胞DNA。使用实时荧光定量PCR进行TRAF2(rs867186)、TAB2(rs237025)和IKBKB(rs13278372) SNP基因分型，并依据制造商推荐方案，采用商品化ELISA试剂盒通过免疫酶学分析检测TRAF2、TAB2、IKBKB蛋白浓度。Ki-67标记指数通过免疫组化分析使用单克隆抗体（克隆号SP6；Spring Bioscience公司）测定。采用"IMB SPSS Statistics 29.0"软件进行统计学数据分析。结果：我们发现两组间TRAF2(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G等位基因频率低于对照组（12.2%对比34.2%，p<0.001）。与AA基因型相比，AG和GG基因型分别使垂体腺瘤发生风险降低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几率降低3.07倍；在隐性模型中，GG基因型使发生几率降低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几率降低2.49倍（p<0.001）。与对照组相比，微腺瘤的基因型分布存在显著差异：81.3%、18.8%、0.0%对比55.3%、20.9%、23.8%（p<0.001），且G等位基因频率更低（9.4%对比34.2%，p<0.001）。在大腺瘤中，基因型分布为78%、16.5%、5.5%对比55.3%、20.9%、23.8%（p<0.001），G等位基因频率亦较低（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几率降低3.5倍（p=0.001），每个G等位基因使微腺瘤发生几率降低3.1倍（p<0.001）。对于大腺瘤，在共显性模型中GG基因型使发生几率降低6.1倍（p<0.001）；与AA基因型相比，GG和AG基因型组合使发生几率降低2.9倍（p<0.001）。隐性模型表明GG基因型使大腺瘤发生几率降低5.3倍（p<0.001），加性模型中每个G等位基因使发生几率降低2.2倍（p<0.001）。结论：与AA基因型相比，TRAF2(rs867186) G等位基因及GG基因型与垂体腺瘤（包括微腺瘤和大腺瘤）发生风险显著降低相关。这些发现提示G等位基因可能对这类肿瘤的发生具有保护作用。
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