CBL 基因多态性与中国人群显微镜下多血管炎易感性的关联：病例对照分析。

Association between CBL gene polymorphism and susceptibility of microscopic polyangiitis in a Chinese population: A case-control analysis.

机构信息

The Second Affiliated Hospital of Guangxi Medical University, Department of Nephrology, Nanning Guangxi, 530007, China; The First Affiliated Hospital, Department of Nephrology, Hengyang Medical School, University of South China, Hengyang Hunan, 421001, China.

The First Affiliated Hospital, Department of Nephrology, Hengyang Medical School, University of South China, Hengyang Hunan, 421001, China.

出版信息

Cytokine. 2024 Jul;179:156596. doi: 10.1016/j.cyto.2024.156596. Epub 2024 Apr 25.

DOI:10.1016/j.cyto.2024.156596

PMID:38669907

Abstract

OBJECTIVE

To assess whether Casitas B-lineage lymphoma (CBL) gene polymorphism influences the risk of microscopic polyangiitis (MPA) in Chinese populations.

METHODS

In total, 266 MPA patients and 297 healthy controls were recruited for a case-control study. Five CBL SNPs were genotyped using multiplex polymerase chain reaction and high-throughput sequencing. The relationship between SNPs and the risk of MPA under different genetic models was evaluated by SNPstats. SNP-SNP interaction was analyzed by generalized multifactor dimensionality reduction (GMDR). Finally, the association between CBL SNPs and treatment effects were assessed.

RESULTS

The results showed that CBL rs2276083 was associated with decreasing MPA risk under dominant (OR: 0.53; p = 0.014) and recessive models (OR: 0.52; p = 0.0034). Stratification analysis indicated that rs2276083 and rs2509671 in age < 60 years, rs2276083 in female or in Han population were protective factors for MPA. The CBL haplotype (A-A-G-C-T) was associated with an increased risk of MPA. GMDR suggested that CBL rs2276083, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) rs1607237, and autophagy-related gene 7 (ATG7) rs7549008 might interact with each other in MPA development (p = 0.0107). CBL rs1047417 with AG genotype and rs11217234 with AG genotype had better clinical treatment effects than other two genotypes (p = 0.048 and p = 0.025, respectively).

CONCLUSION

The genetic polymorphism of CBL had a potential association with the risk of MPA and clinical treatment effects in Guangxi population in China.

摘要

目的

评估 Casitas B 细胞淋巴瘤（CBL）基因多态性是否会影响中国人群中显微镜下多血管炎（MPA）的发病风险。

方法

采用病例对照研究，共纳入 266 例 MPA 患者和 297 例健康对照者。采用多重聚合酶链反应和高通量测序技术对 5 个 CBL 单核苷酸多态性（SNP）进行基因分型。采用 SNPstats 评估 SNP 在不同遗传模型下与 MPA 发病风险的关系。采用广义多因子降维分析（GMDR）分析 SNP-SNP 相互作用。最后，评估 CBL SNPs 与治疗效果的关系。

结果

结果表明，CBL rs2276083 与显性（OR：0.53；p=0.014）和隐性（OR：0.52；p=0.0034）模型下 MPA 发病风险降低有关。分层分析表明，rs2276083 和 rs2509671 在年龄<60 岁、女性或汉族人群中为 MPA 的保护因素。CBL 单倍型（A-A-G-C-T）与 MPA 发病风险增加有关。GMDR 提示 CBL rs2276083、磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α（PI3KCA）rs1607237 和自噬相关基因 7（ATG7）rs7549008 可能在 MPA 发病机制中存在相互作用（p=0.0107）。CBL rs1047417 的 AG 基因型和 rs11217234 的 AG 基因型比其他两种基因型的临床治疗效果更好（p=0.048 和 p=0.025）。