（rs2234663）和（rs1143627、rs16944）基因变体及白细胞介素-1β水平与结直肠癌的关联：实验研究和计算机模拟分析

Association of Variants in (rs2234663) and (rs1143627, rs16944) and Interleukin-1β Levels with Colorectal Cancer: Experimental Study and In Silico Analysis.

作者信息

Gallegos-Arreola Martha Patricia, Garibaldi-Ríos Asbiel Felipe, Gutiérrez-Hurtado Itzae Adonaí, Zúñiga-González Guillermo Moisés, Figuera Luis E, Gómez-Meda Belinda Claudia, Puebla-Pérez Ana María, García-Ortiz José Elías, Delgado-Saucedo Jorge I, Castro-García Paola Beatriz, Rentería-Ramírez María de Jesús, Torres-Mendoza Blanca Miriam

机构信息

División de Genética, Centro de Investigación Biomédica de Occidente, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Jalisco, Mexico.

Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico.

出版信息

Genes (Basel). 2024 Nov 27;15(12):1528. doi: 10.3390/genes15121528.

DOI:10.3390/genes15121528

PMID:39766795

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11675222/

Abstract

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is a multifactorial disease where the inflammatory state is crucial. This study analyzes the association of the IL-1RN (rs2234663) and IL-1β (rs1143627, rs16944) variants and IL-1β levels with CRC.

METHODS

This study included 230 CRC patients and 256 controls. Genotypes were determined by PCR and plasma IL-1β levels by ELISA. RegulomeDB analyzed the variants' functional impacts, while OncoDB assessed and expression's influence on CRC.

RESULTS

The A1A1 genotype and dominant pattern of the rs2234663 variant were risk factors for CRC, whereas the A1A2 genotype showed a protective effect. The TC genotype of the rs1143627 variant and the T allele of rs16944 were associated with increased risk, whereas the C allele had a protective effect. The A1A1 genotype was associated with stage I-II CRC diagnosis, while the A2A2 genotype was associated with stage III-IV and ethanol consumption. The CC genotype of rs1143627 was associated with people younger than 50 years and tobacco use, and the TCCC genotype was related to stage III-IV stages and metastasis and hemorrhoids ( < 0.05). IL-1β levels were not associated with CRC. In silico analysis revealed that the variants are in located in important regions regulatory of genes. Elevated and mRNA levels were found in CRC, linked to clinicopathological features of the disease.

CONCLUSIONS

The analyzed variants are associated with CRC and may influence gene regulation by being located at critical sites of key genetic regulators.

摘要

背景/目的：结直肠癌（CRC）是一种多因素疾病，炎症状态至关重要。本研究分析白细胞介素-1受体拮抗剂（IL-1RN，rs2234663）和白细胞介素-1β（IL-1β，rs1143627、rs16944）基因变异以及IL-1β水平与结直肠癌的关联。

方法

本研究纳入230例结直肠癌患者和256例对照。通过聚合酶链反应（PCR）确定基因型，采用酶联免疫吸附测定（ELISA）检测血浆IL-1β水平。调控组数据库（RegulomeDB）分析变异的功能影响，肿瘤数据库（OncoDB）评估和表达对结直肠癌的影响。

结果

rs2234663变异的A1A1基因型和显性模式是结直肠癌的危险因素，而A1A2基因型具有保护作用。rs1143627变异的TC基因型和rs16944的T等位基因与风险增加相关，而C等位基因具有保护作用。A1A1基因型与Ⅰ-Ⅱ期结直肠癌诊断相关，而A2A2基因型与Ⅲ-Ⅳ期及乙醇摄入相关。rs1143627的CC基因型与年龄小于50岁及吸烟相关，TCCC基因型与Ⅲ-Ⅳ期、转移及痔疮相关（P<0.05）。IL-1β水平与结直肠癌无关。计算机分析显示，这些变异位于基因的重要调控区域。在结直肠癌中发现和信使核糖核酸（mRNA）水平升高，与疾病的临床病理特征相关。