Ghafoor Dlzar Dlshad, Ahmed Dlshad Omar, Al-Bajalan Sarwer Jamal
Medical Laboratory Science Department, Komar University of Science and Technology, Sulaymaniyah, 46001, Iraq.
Department of Chemistry, University of Sulaimani, College of Science, Sulaymaniyah, 46001, Iraq.
J Mol Neurosci. 2025 Aug 2;75(3):95. doi: 10.1007/s12031-025-02386-9.
This is the first study in Iraq to integrate socioeconomic, genetic, and oxidative stress markers in MS patients, revealing unique associations between HLA-DRB1 polymorphisms and relapsing-remitting MS (RRMS). This work investigated the demographic, clinical, oxidative stress, and molecular aspects influencing quality of life in multiple sclerosis patients in Sulaymaniyah, Iraq. A cross-sectional study was undertaken with 63 MS patients and 20 healthy controls to evaluate quality of life using the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire. We compiled demographic and clinical information, including age, sex, educational level, socioeconomic level, multiple sclerosis phenotype, disease duration, and Expanded Disability Status Scale (EDSS) scores. In this work, single nucleotide polymorphism (SNP) of HLA-DRB1 was investigated in conjunction with oxidative stress markers, including MDA, 8-OHdG, and GPx activity, to the expression of the NRF2 gene. Significant relationships (p < 0.05) between quality of life and crucial variables, including the degree of the disease, level of education, socioeconomic level, and oxidative stress markers, were revealed by statistical analysis. MDA and 8-OHdG levels tightly predicted NRF2 expression (R = 0.713, p < 0.001 according to regression analysis). This result draws attention to an antioxidant response seeking to offset its lack of potency. All MS subtypes showed noticeably higher NRF2 expression than controls, according to post hoc analysis. PPMS showed the highest overexpression (p < 0.001). The results indicated the importance of oxidative stress markers in multiple sclerosis and how it affects quality of life. For this reason, personalized treatments must target both oxidative stress and socioeconomic status to help patients get better, especially in underdeveloped areas. Besides this, the study offers important information for legislators and medical practitioners creating thorough, patient-centered care plans to improve MS management. Furthermore, serum vitamin D3 levels varied greatly among MS subtypes (p = 0.008); PPMS patients had the lowest levels. Though p = 0.162, vitamin B12 levels did not approach statistical relevance; lower levels were observed in progressive MS forms, implying a possible function in disease pathogenesis. In this work, single nucleotide polymorphism (SNP) of HLA-DRB1 has been investigated together with oxidative stress markers including MDA, 8-OHdG, and GPx activity to NRF2 gene expression. Two RRMS patients showed the T risk allele (G > A transition at rs3135), indicating a possible genetic predisposition to MS in this cohort based on SNP analysis. Moreover, MS patients and healthy controls underwent genotyping analysis utilizing Sanger sequencing to evaluate the distribution of HLA-DRB1 rs3135388. More often detected in MS subtypes, especially in RRMS forms, the T allele supports a genetic susceptibility connected to oxidative stress dysregulation.
这是伊拉克第一项整合社会经济、遗传和氧化应激标志物对多发性硬化症（MS）患者进行研究，揭示了HLA - DRB1基因多态性与复发缓解型多发性硬化症（RRMS）之间独特的关联。这项研究调查了影响伊拉克苏莱曼尼亚多发性硬化症患者生活质量的人口统计学、临床、氧化应激和分子方面的因素。对63例MS患者和20名健康对照进行了横断面研究，使用多发性硬化症生活质量-54（MSQoL - 54）问卷评估生活质量。我们收集了人口统计学和临床信息，包括年龄、性别、教育水平、社会经济水平、多发性硬化症表型、病程以及扩展残疾状态量表（EDSS）评分。在这项研究中，研究了HLA - DRB1的单核苷酸多态性（SNP），并结合氧化应激标志物，包括丙二醛（MDA）、8 - 羟基脱氧鸟苷（8 - OHdG）和谷胱甘肽过氧化物酶（GPx）活性，以及NRF2基因的表达。统计分析揭示了生活质量与关键变量之间的显著关系（p < 0.05），这些关键变量包括疾病程度、教育水平、社会经济水平和氧化应激标志物。MDA和8 - OHdG水平紧密预测NRF2表达（根据回归分析，R = 0.713，p < 0.001）。这一结果引起了人们对寻求抵消其效力不足的抗氧化反应的关注。根据事后分析，所有MS亚型的NRF2表达均明显高于对照组。原发性进展型多发性硬化症（PPMS）表现出最高的过表达（p < 0.001）。结果表明氧化应激标志物在多发性硬化症中的重要性以及它如何影响生活质量。因此，个性化治疗必须针对氧化应激和社会经济状况，以帮助患者改善病情，特别是在欠发达地区。除此之外，该研究为立法者和医疗从业者制定全面的、以患者为中心的护理计划以改善MS管理提供了重要信息。此外，血清维生素D3水平在MS亚型之间差异很大（p = 0.008）；PPMS患者的水平最低。尽管p = 0.162，但维生素B12水平未达到统计学相关性；在进展型MS形式中观察到较低水平，这意味着其在疾病发病机制中可能发挥作用。在这项研究中，研究了HLA - DRB1的单核苷酸多态性（SNP），并结合氧化应激标志物，包括MDA、8 - OHdG和GPx活性以及NRF2基因表达。两名RRMS患者显示出T风险等位基因（rs3135处G > A转换），基于SNP分析表明该队列中MS可能存在遗传易感性。此外，MS患者和健康对照利用桑格测序进行基因分型分析，以评估HLA - DRB1 rs3135388的分布。T等位基因在MS亚型中更常被检测到，尤其是在RRMS形式中，这支持了与氧化应激失调相关的遗传易感性。
