Two polymorphic mutations in promoter region of DNA polymerase β in relatively higher percentage of thymic hyperplasia patients

BACKGROUND: DNA polymerase β is one of the key enzymes involved in the repair of DNA damage, and its high or low expression is closely related to tumorigenesis. In a previous study on lung cancer, we found three genetic mutations in the promoter region of the Polb gene could be detected in the Han Chinese population. The purpose of this study was to explore the relationship between these mutations and thymic hyperplasia. METHODS: Genomic DNA was extracted from 59 thymic hyperplasia patients by the salting out method and used for amplification of the promoter region of the Polb gene. The Polb gene mutation and its frequency were analyzed systematically by comparing them with the deposited wild‐type gene sequence in the NCBI database. The three typical mutated sequences in the promoter region of Polb gene, ‐196G > T, ‐168C > A and ‐188_‐187insCGCCC, were then amplified and ligated to pGL4.10 vector, so as to get the vectors used for the infection of 293T cells to explore their transcription activities by dual‐luciferase reporter system. RESULTS: Two types of mutations, ‐168C>A and‐188_‐187insCGCCC, were found in a significantly higher percentage in patients with thymic hyperplasia than in normal healthy people after sequencing analysis of 59 patients and 60 healthy controls. These results suggest that the two mutations may be closely related to thymic hyperplasia. in vitro functional experiments showed that‐168C>A could significantly increase promoter activity, whereas ‐188_‐187insCGCCC could significantly reduce promoter activity, suggesting that these two mutations may affect the expression level of the Polb gene in cells. CONCLUSIONS: Two types of mutations in the promoter region of the Polb gene, ‐168C>A and‐188_‐187insCGCCC, are associated with thymic hyperplasia and may become a new risk factor for this disease. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Genetic mutations in the Polb gene are reported to be associated with different kinds of cancers. However, their relationship with thymic hyperplasia is still unclear. WHAT THIS STUDY ADDS: For the first time, we report that two nucleotide mutations in the promoter region of the Polb gene are closely related with thymic hyperplasia after sequencing 59 patients and 60 healthy controls in the Han Chinese population.