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PARP - 1基因启动子区域可能与多发性硬化症的病情进展有关。

PARP-1 gene promoter region may be associated with progression in multiple sclerosis.

作者信息

Yilmaz Busra, Genc Gunes Cakmak, Celik Sevim Karakas, Cinar Bilge Piri, Acikgoz Mustafa, Dursun Ahmet

机构信息

Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.

Department of Medical Genetics, Zonguldak Bulent Ecevit University, Zonguldak, Turkey.

出版信息

Clin Chim Acta. 2025 May 15;572:120275. doi: 10.1016/j.cca.2025.120275. Epub 2025 Mar 30.

Abstract

Multiple Sclerosis (MS) is a leading cause of disability among young adults. Most cases begin with relapsing-remitting MS (RRMS) and can transition to secondary progressive MS (SPMS) over time. It is known that the inflammatory status of the central nervous system changes during the progression of MS. Poly (ADP-ribose) polymerase-1 (PARP-1) is an enzyme involved in several cellular processes. Our study aimed to investigate the relationship between MS and the PARP-1 gene. We analyzed the PARP-1 gene's missense polymorphism rs1136410, promoter region polymorphism rs7527192, and 3'UTR polymorphism rs8679 in 123 MS patients and 168 healthy controls using the PCR-RFLP method. We examined genotype and allele frequency distributions among case-control groups and clinical subgroups. We observed that the CC genotype of rs7527192 polymorphism was increased in SPMS patients compared to controls. We also found that the CC genotype and C allele frequency were increased in the EDSS score > 3-6 group compared to healthy controls. The C allele frequency was increased in EDSS score > 3-6 compared to those with ≤ 3 and ≥ 6. When the results observed in our study are evaluated with the known effect of PARP-1 on the inflammasome pathway, we suggest that rs7527192 may be effective in the progression process through the activity of the PARP-1 inflammasome pathway.

摘要

多发性硬化症(MS)是导致年轻人残疾的主要原因之一。大多数病例始于复发缓解型多发性硬化症(RRMS),并可能随着时间的推移转变为继发进展型多发性硬化症(SPMS)。已知在MS进展过程中,中枢神经系统的炎症状态会发生变化。聚(ADP-核糖)聚合酶-1(PARP-1)是一种参与多种细胞过程的酶。我们的研究旨在探讨MS与PARP-1基因之间的关系。我们采用PCR-RFLP方法分析了123例MS患者和168例健康对照中PARP-1基因的错义多态性rs1136410、启动子区域多态性rs7527192和3'UTR多态性rs8679。我们检查了病例对照组和临床亚组中的基因型和等位基因频率分布。我们观察到,与对照组相比,SPMS患者中rs7527192多态性的CC基因型增加。我们还发现,与健康对照相比,扩展残疾状态量表(EDSS)评分>3-6组中的CC基因型和C等位基因频率增加。与EDSS评分≤3和≥6的患者相比,EDSS评分>3-6的患者中C等位基因频率增加。当结合PARP-1对炎性小体途径的已知作用来评估我们研究中观察到的结果时,我们认为rs7527192可能通过PARP-1炎性小体途径的活性在疾病进展过程中发挥作用。

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