Age and Gender Related Changes in Human Parotid Gland Gene Expression

Previous studies suggest that there may be age and gender related differences in salivary gland function. However, the limited and often conflicting information available from healthy populations makes it difficult to confirm these differences. The purpose of the present study was to evaluate and compare changes in gene expression associated with age and gender in the human parotid gland. Differential expression, defined as statistically significant differences with at least 1.5 fold changes, was detected using the Affymetrix® GeneChip® HGU133plus2.0 microarray in 787 gene probe sets; 320 showed higher expression in males, while 467 showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid gland including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A, syntaxin binding protein STXBP1. When the gene expression results from the youngest (19-38 years old) and the oldest (65-69 years old) female subjects were further evaluated, it was found that the expression of 228 genes were altered during aging; 155 genes were down-regulated, whereas 73 genes were up-regulated in the female parotid gland. Of the genes that were altered during aging, 24 of the 28 genes (86%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for further study by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix array and quantitative, real-time RT-PCR methods. Taken together, our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the down regulation of several categories of genes. Moreover, the gender specific gene expressions identified in the present study correlates with the previously observed sexual dimorphism in salivary gland function. Keywords: Human Parotid Gland Human parotid glands were obtained from healthy male and female subjects (19-85 years of age). 3 young female parotid glands were compared with 3 older female parotid gland. 8 Female samples were compared with 5 male samples

既往研究表明，唾液腺（salivary gland）功能可能存在与年龄和性别相关的差异。然而，现有来自健康人群的相关资料既有限且常存在矛盾，难以证实上述差异。本研究旨在评估并比较人类腮腺（human parotid gland）中与年龄、性别相关的基因表达变化。研究采用Affymetrix® GeneChip® HGU133plus2.0微阵列芯片，在787个基因探针集中检测到差异表达基因（定义为具备统计学显著性差异且表达倍数变化≥1.5）；其中320个基因在男性组织中表达更高，467个基因在女性组织中表达更高。多种与唾液分泌相关的基因在男女腮腺组织中呈现差异表达，包括囊泡相关膜蛋白3（vesicle-associated membrane protein 3, VAMP3）、突触体相关蛋白23（synaptosomal-associated protein 23, SNAP23）、RAS癌基因家族成员RAB1A、Syntaxin结合蛋白1（STXBP1）。进一步分析最年轻（19~38岁）与最年长（65~69岁）女性受试者的基因表达结果后发现，女性腮腺组织中有228个基因的表达随衰老发生改变：155个基因表达下调，73个基因表达上调。在随衰老出现表达改变的基因中，归类为与免疫应答相关的28个基因中有24个（占比86%）在老年腮腺组织中表达下调。研究选取一组与年龄、性别相关的差异表达基因，通过实时定量逆转录聚合酶链反应（quantitative real-time RT-PCR）开展后续验证。Affymetrix微阵列与实时定量RT-PCR两种方法检测到的基因表达差异结果具有良好一致性。综上，本研究数据表明，老年人群的唾液腺功能可能受到不利影响，这至少部分归因于多类基因的表达下调。此外，本研究中鉴定出的性别特异性基因表达模式，与此前观察到的唾液腺功能性别二态性相一致。关键词：人类腮腺（Human Parotid Gland）本研究的人类腮腺组织取自健康男女受试者（年龄范围19~85岁）。将3例年轻女性腮腺组织与3例老年女性腮腺组织进行对比；将8例女性样本与5例男性样本进行对比。