印度喀拉拉邦的II类人类白细胞抗原（DRB1和DQB1）等位基因、白细胞介素7受体（rs6897932）变体与多发性硬化症风险
Class II HLA (DRB1, & DQB1) alleles and IL7R (rs6897932) variants and the risk for Multiple Sclerosis in Kerala, India.
作者信息
Vinoy Navia, Sheeja Neethu, Kumar Suresh, Biswas Lalitha
机构信息
Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Ponekkara, Kochi, Kerala 682041, India.
Department of Neurology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala 682041, India.
出版信息
Mult Scler Relat Disord. 2021 May;50:102848. doi: 10.1016/j.msard.2021.102848. Epub 2021 Feb 20.
BACKGROUND
Different human leukocyte antigen (HLA) variants are known to modulate the risk of multiple sclerosis. The main objective of this study was to identify HLA-DRB1 and HLA-DQB1 alleles and Non -HLA gene IL7R (rs6897932) variants associated with MS.
METHODS
Patients attending the MS clinic, diagnosed with Multiple Sclerosis as per Mc Donald diagnostic criteria were the subjects in the study. The association of the highly polymorphic HLA-DRB1 and HLA-DQB1 loci was determined by high resolution tissue typing and the genotyping of the IL7R (rs6897932) variants was performed by Sanger sequencing in MS patients (n = 81) and healthy individuals (n = 82).
RESULTS
HLA-DRB115:01/15:02 alleles (OR = 3.65; p< 0.0001) and HLA-DQB106:02 (OR=4.19, p<0.0001) were found to be positively associated while HLA-DRB114:04:01 (OR = 0.21; p = 0.0009) was found to be negatively associated with MS. The most significant predisposing HLA haplotype was found to be DRB115:01-DQB106:02 (OR=5.69, p<0.0001). Univariate analysis of IL7R SNP (rs6897932) showed no significant association with MS in our population whereas analysis of HLA-DRB1 alleles and IL7R (rs6897932) genotypes showed significant association between the HLA-DRB115:01/15:02 and the IL7R (rs6897932) CC genotype (OR = 3.58, p = 0.0002).
CONCLUSION
HLA-DRB115:01, 15:02 and DQB106:02 are the predisposing alleles while HLA-DRB1*14:04 is the protective allele for MS in our population.
背景
已知不同的人类白细胞抗原（HLA）变体可调节多发性硬化症的风险。本研究的主要目的是鉴定与多发性硬化症相关的HLA - DRB1和HLA - DQB1等位基因以及非HLA基因IL7R（rs6897932）变体。
方法
根据麦克唐纳诊断标准被诊断为多发性硬化症的多发性硬化症门诊患者为研究对象。通过高分辨率组织分型确定高度多态性的HLA - DRB1和HLA - DQB1位点的关联，并通过桑格测序对81例多发性硬化症患者和82例健康个体进行IL7R（rs6897932）变体的基因分型。
结果
发现HLA - DRB115:01/15:02等位基因（OR = 3.65；p < 0.0001）和HLA - DQB106:02（OR = 4.19，p < 0.0001）呈正相关，而HLA - DRB114:04:01（OR = 0.21；p = 0.0009）与多发性硬化症呈负相关。发现最显著的易患HLA单倍型为DRB115:01 - DQB106:02（OR = 5.69，p < 0.0001）。对IL7R单核苷酸多态性（rs6897932）的单变量分析显示，在我们的人群中与多发性硬化症无显著关联，而对HLA - DRB1等位基因和IL7R（rs6897932）基因型的分析显示，HLA - DRB115:01/15:02与IL7R（rs6897932）CC基因型之间存在显著关联（OR = 3.58，p = 0.0002）。
结论
在我们的人群中，HLA - DRB115:01、15:02和DQB106:02是多发性硬化症的易感等位基因，而HLA - DRB1*14:04是保护等位基因。
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