冻结肩与正常人IL-1和受体拮抗剂的基因多态性△

Genetic polymorphism of IL-1 and receptor antagonists in frozen shoulder and normal subjects

摘要:

[目的] 探索冻结肩（frozen shoulder, FS） 与IL-1β 和白细胞介素-1 受体拮抗剂（interleukin-1 receptor antagonist,IL-1Ra） 的基因多态性的相关性。[方法] 选取2021 年1 月—2023 年8 月在青岛市胶州中心医院就诊的225 例原发性或有该病病史的患者为冻结肩组，另275 名正常人为正常组。通过聚合酶链反应和限制性片段长度多态性方法检测两组IL-1β 基因位点的基因型，分析其单倍体与冻结肩患病风险率之间的相关性，并分析IL-1 受体拮抗剂等位基因2（interleukin-l receptor an-tagonist allele*2, IL-1RN） 不同基因型与冻结肩患病易感性的相关性。[结果] 与野生型CC（未发生基因突变的基因型） 相比，杂合子CT 基因型（发生基因突变） 的患者发生FS 的风险显著升高（OR=1.952, 95%CI 1.142~3.320, P=0.014），同时，IL-1B+3954 位点的C 基因可能是保护基因，IL-1B+3954 位点具有C 基因发生FS 的风险显著降低（OR=0.577, 95%CI 0.309~0.987, P=0.049）。IL-1B-31C/T 位点CT 基因型发生FS 的风险显著高于TT 型（OR=1.791, 95%CI 1.171~2.742, P=0.004)。单倍体型分析发现，与最常见的CCT 单体型相比较，单体型TTT 与FS 高风险发病率具有更强的相关性（OR=7.100, 95%CI 1.492~33.870，P=0.014）。经非条件逻辑回归分析发现，IL-1RN（VNTR） 的4 种基因在两组之间的分布差异无统计学意义（P=0.521），IL-1RN基因变异型组（1/2 和2/2） 发生FS 的风险是非变异组（1/1、1/3、1/4） 的1.895 倍，但结果差异无统计学意义（P＞0.05）。[结论] 在冻结肩组中IL-1β 基因rs1143627 与rs1143634 位点的CT 基因型与冻结肩的易感性相关；由3 个基因位点形成的单倍体型TTT 可能会增加罹患冻结肩的风险，在IL-1RN 中未发现冻结肩的易感基因型。

Abstract:

[Objective] To explore the relationship between frozen shoulder (FS) and gene polymorphism of IL-1β and interleukin-1receptor antagonist (IL-1Ra). [Methods] From January 2021 to August 2023, 225 patients who were treated in our hospital were selected asthe frozen shoulder group, while other 275 normal persons as the normal group. The genotypes of the two groups in IL-1β gene loci were de-tected by polymerase chain reaction and restriction fragment length polymorphism. The correlation between the haploids and the risk rate offrozen shoulder disease was analyzed. In addition, the correlation between different genotypes of interleukin-l receptor antagonist allele*2,(IL-1RN) and the susceptibility to frozen shoulder disease was also analyzed. [Results] Compared with wild-type CC (non-mutated geno-type), patients with heterozygous CT genotype (mutated genotype) had a significantly higher risk of FS (OR=1.952, 95%CI 1.142~3.320, P=0.014). The C gene at the IL-1B+3954 locus may be a protective gene, and the risk of FS in the C gene was significantly reduced at the IL-1B+3954 locus (OR=0.577, 95%CI 0.309~0.987, P=0.049). The risk of FS for CT genotype at IL-1B-31C/T locus was significantly higherthan that for TT genotype (OR=1.791, 95%CI 1.171~2.742, P=0.004). Haplotype analysis found that haplotype TTT was more strongly asso-ciated with a higher risk of FS than the most common CCT haplotype (OR=7.100, 95%CI 1.492~33.870, P=0.014). Unconditional Logisticregression analysis showed that there was no statistically significant difference in the distribution of four genes of IL-1RN (VNTR) betweenthe two groups (P=0.521), and the risk of FS in the IL-1RN variant group (1/2 and 2/2) was 1.895 times higher than that in the non-variantgroup (1/1, 1/3, 1/4), whereas which was not statistically significant (P＞0.05). [Conclusion] CT genotypes of IL-1β gene rs1143627 andrs1143634 were associated with susceptibility to frozen shoulder in frozen shoulder group. Haploid TTT formed by three gene loci may in-crease the risk of frozen shoulder, and no susceptibility genotype for frozen shoulder was found in IL-1RN.