Abdollah Zadeh Rasoul, Jalilian Nazanin, Sahraian Mohammad Ali, Kasraian Zeinab, Noori-Daloii Mohammad Reza
a Department of Medical Genetics, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
b Department of Clinical Biochemistry, School of Medicine , Kermanshah University of Medical Sciences , Kermanshsh , Iran.
Neurol Res. 2017 Mar;39(3):217-222. doi: 10.1080/01616412.2016.1278108. Epub 2017 Jan 12.
Multiple sclerosis (MS) is the most prevalent disorder of nervous system inflammation which involves demyelination of spinal cord; this process depends on both environmental and genetic susceptibility factors. In the present study, we examined the association between two SNPs in RPS6KB1 (rs180515) and CD86 (rs9282641) with MS in Iranian population. RPS6KB1gene encodes p70S6K1 protein which plays a key role in mTOR signaling pathway, while CD86 gene codes a membrane protein type I which belongs to immunoglobulin super family act on co-stimulation signaling pathway.
In this case-control study 130 patients with MS and 128 matched healthy controls were enrolled, genomic DNA was isolated and genotyping was performed using mismatched PCR-RFLP. The results were finally analyzed using SPSS.
Our results showed significant difference in allelic frequency of SNP rs180515 among cases and controls (P = 0.004). For this variation, AA genotype was shown to have protective effect (P = 0.016 and OR = 0.6), while GG genotype was a susceptive genotype to MS (P = 0.04 and OR = 2.2). Allelic frequency of SNP rs9282641 also showed significant difference between cases and controls (P = 0.006). For this SNP, AG genotype had predisposing effect (P = 0.04, OR = 2.3), and GG genotype showed protective (P = 0.01, OR = 0.411).
We successfully replicated the association of two novel SNPs introduced by a GWAS study, and MS in the Iranian population. This result can open ways for better understanding the mechanisms involved in MS.
多发性硬化症（MS）是最常见的神经系统炎症性疾病，涉及脊髓脱髓鞘；这一过程取决于环境和遗传易感性因素。在本研究中，我们检测了伊朗人群中核糖体蛋白S6激酶β1（RPS6KB1，rs180515）和CD86（rs9282641）基因的两个单核苷酸多态性（SNP）与MS的关联。RPS6KB1基因编码p70S6K1蛋白，其在mTOR信号通路中起关键作用，而CD86基因编码一种I型膜蛋白，属于免疫球蛋白超家族，作用于共刺激信号通路。
在这项病例对照研究中，招募了130例MS患者和128例匹配的健康对照，分离基因组DNA，并使用错配聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行基因分型。最终使用社会科学统计软件包（SPSS）分析结果。
我们的结果显示，病例组和对照组中SNP rs180515的等位基因频率存在显著差异（P = 0.004）。对于该变异，AA基因型显示出保护作用（P = 0.016，比值比[OR]=0.6），而GG基因型是MS的易感基因型（P = 0.04，OR = 2.2）。SNP rs9282641的等位基因频率在病例组和对照组之间也显示出显著差异（P = 0.006）。对于该SNP，AG基因型具有易感性（P = 0.04，OR = 2.3），而GG基因型显示出保护作用（P = 0.01，OR = 0.411）。
我们成功重复了一项全基因组关联研究（GWAS）中引入的两个新SNP与伊朗人群中MS的关联。这一结果可为更好地理解MS的发病机制开辟道路。
