Influence of polymorphisms on the phenotype of TLR1, TLR4 and TLR9 genes and their association with cervical cancer: Bioinformatics prediction analysis and a case-control study

IF 1.4 4区医学 Q4 GENETICS & HEREDITY

Cancer Genetics Pub Date : 2024-10-10 DOI:10.1016/j.cancergen.2024.10.001

Edilson Leite de Moura , Israel Faustino dos Santos , Paulo Pedro de Freitas , Denise Macedo da Silva , Ana Caroline Melo dos Santos , Aline Cristine Pereira e Silva , Abel Barbosa Lira Neto , Rubens Pessoa de Barros , Jhonatan David Santos das Neves , Nirliane Ribeiro Barbosa , Carolinne de Sales Marques , Carlos Alberto de Carvalho Fraga , Karol Fireman de Farias , Elaine Virginia Martins de Souza Figueiredo

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引用次数: 0

Abstract

Susceptibility to cervical cancer has been associated with Toll-like receptors (TLRs), which is an important component of innate immunity. According to previous studies, polymorphisms in TLRs genes can affect immune response pathways and lead to the development of cervical cancer. The present study aims to evaluate the functionality of polymorphisms in TLR1, TLR4 and TLR9 genes and their associations with cervical cancer. To identify the functionality of polymorphisms, we used the following tools: MUpro, ChimeraX, SNP2TFBS and GTEx. A case-control study including 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls was conducted in the Brazilian population. Polymorphisms genotyping was performed by real-time PCR, using TaqMan probes, using the allelic discrimination method. Bioinformatics prediction showed that the TLR1 rs4833095 [NM_003263.4 (TLR1):c.743T>C (p.Asn248Ser)] and TLR4 rs4986790 [NM_138554.5 (TLR4):c.896A>G (p.Asp299Gly)] polymorphisms alter the structure and stability of their respective proteins. TLR9 rs187084 [NM_017442.3(TLR9):c.-1486A>G] polymorphism seems to affect the THAP1 binding site and modify gene expression. In the case-control study, the c.743TC heterozygous genotype of the rs4833095 SNP in the TLR1 gene was associated with an increased risk for HSIL/cervical cancer. No association of TLR4 rs4986790 and TLR9 rs187084 SNPs with HSIL/cervical cancer was found in the studied population. Allelic combination CAG (rs4833095/ rs4986790/ rs187084) increased the risk of cervical cancer. In conclusion, the present study identified that polymorphisms in TLRs genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.

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多态性对 TLR1、TLR4 和 TLR9 基因表型的影响及其与宫颈癌的关系：生物信息学预测分析和病例对照研究

宫颈癌的易感性与 Toll 样受体（TLRs）有关，而 Toll 样受体是先天性免疫的重要组成部分。根据以往的研究，TLRs 基因的多态性会影响免疫反应途径，并导致宫颈癌的发生。本研究旨在评估 TLR1、TLR4 和 TLR9 基因多态性的功能及其与宫颈癌的关联。为确定多态性的功能，我们使用了以下工具：MUpro、ChimeraX、SNP2TFBS 和 GTEx。我们在巴西人群中进行了一项病例对照研究，其中包括 57 例病例（11 例高级别上皮内病变（HSIL）和 46 例宫颈癌）和 67 例临床健康对照。使用 TaqMan 探针和等位基因鉴别方法，通过实时 PCR 进行多态性基因分型。生物信息学预测显示，TLR1 rs4833095 [NM_003263.4 (TLR1):c.743T>C（p.Asn248Ser）] 和 TLR4 rs4986790 [NM_138554.5 (TLR4):c.896A>G（p.Asp299Gly）] 多态性改变了各自蛋白质的结构和稳定性。TLR9 rs187084 [NM_017442.3(TLR9):c.-1486A>G] 多态性似乎会影响 THAP1 结合位点并改变基因表达。在病例对照研究中，TLR1 基因中 rs4833095 SNP 的 c.743TC 杂合基因型与 HSIL/宫颈癌风险增加有关。在研究人群中，未发现 TLR4 rs4986790 和 TLR9 rs187084 SNP 与 HSIL/宫颈癌有关。等位基因组合 CAG（rs4833095/ rs4986790/ rs187084）增加了宫颈癌的患病风险。总之，本研究发现 TLRs 基因的多态性会影响其各自基因的表型，并导致 HSIL 或宫颈癌的发生。

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来源期刊

Cancer Genetics ONCOLOGY-GENETICS & HEREDITY

CiteScore

3.20

自引率

5.30%

发文量

167

审稿时长

27 days

期刊介绍： The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor.