Zhang Jingjing, Peng Chenxing, Xu Shuo, Zhao Yufei, Zhang Xiaoyun, Zhang Shasha, Guo Zhanjun
Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Immunology and Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Int J Rheum Dis. 2023 Nov;26(11):2157-2162. doi: 10.1111/1756-185X.14876. Epub 2023 Aug 18.
The pathogenesis of ankylosing spondylitis (AS) seems to be associated with genetics, the environment, heredity, and oxidative stress. Single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) region of mitochondrial DNA (mtDNA) and mtDNA copy number were investigated for their correlation with AS patients.
This study included 83 AS patients and 100 healthy controls from the Second Hospital of Hebei Medical University. DNAs were extracted from blood samples for polymerase chain reaction analysis and quantitative real-time polymerase chain reaction analysis. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology.
The distribution frequencies of the minor alleles of nucleotides 16304C (p = .037), 16311C (p = .027), and 152C (p = .034) were remarkably higher in AS patients than in healthy controls, which indicated that the16304C, 16311C, and 152C alleles were correlated with an increased risk of AS. Simultaneously, mtDNA copy number was statistically higher in patients with AS compared with controls (1.450 ± 0.876 versus 0.835 ± 0.626, p < .001). We also observed an increased ROS generation in AS patients compared with controls (27 066.169 ± 18 364.819 versus 14 758.330 ± 5854.946, p < .001) subsequently. In addition, the AS susceptible SNP 16311C is associated with high ROS levels (35 065.177 ± 26 999.934 vs. 25 005.818 ± 14 999.495, p = .043).
Our study demonstrated that SNPs in the mtDNA D-loop could be AS risk biomarkers with the potential to promote oxidative stress levels; mtDNA copy number-induced mitochondrial dysfunction may also be involved in AS pathogenesis.
强直性脊柱炎（AS）的发病机制似乎与遗传、环境、遗传因素及氧化应激相关。本研究探讨线粒体DNA（mtDNA）置换环（D环）区域的单核苷酸多态性（SNP）及mtDNA拷贝数与AS患者的相关性。
本研究纳入河北医科大学第二医院的83例AS患者和100例健康对照。从血样中提取DNA，进行聚合酶链反应分析和定量实时聚合酶链反应分析。采用荧光探针技术检测血浆活性氧（ROS）水平。
核苷酸16304C（p = 0.037）、16311C（p = 0.027）和152C（p = 0.034）的次要等位基因在AS患者中的分布频率显著高于健康对照，表明16304C、16311C和152C等位基因与AS风险增加相关。同时，AS患者的mtDNA拷贝数在统计学上高于对照组（1.450±0.876 vs. 0.835±0.626，p < 0.001）。随后我们还观察到，与对照组相比，AS患者的ROS生成增加（27066.169±18364.819 vs. 14758.330±5854.946，p < 0.001）。此外，AS易感SNP 16311C与高ROS水平相关（35065.177±26999.934 vs. 25005.818±14999.495，p = 0.043）。
我们的研究表明，mtDNA D环中的SNP可能是AS风险生物标志物，具有促进氧化应激水平的潜力；mtDNA拷贝数诱导的线粒体功能障碍也可能参与AS的发病机制。
