Ordoñez Graciela, Romero Sandra, Orozco Lorena, Pineda Benjamín, Jiménez-Morales Silvia, Nieto Alejandra, García-Ortiz Humberto, Sotelo Julio
National Institute of Neurology and Neurosurgery of Mexico, Insurgentes Sur #3877, Mexico City 14269, Mexico.
National Institute of Genomic Medicine of Mexico, Periférico Sur 4809, Mexico City 14610, Mexico.
Clin Neurol Neurosurg. 2015 Mar;130:55-60. doi: 10.1016/j.clineuro.2014.11.026. Epub 2014 Dec 24.
Multiple sclerosis (MS) is a complex immune-mediated disease. It has been suggested that genetic factors could explain differences in the prevalence among ethnic groups. To know whether genetic ancestry is a potential risk factor for MS in Mexican patients and to identify candidate genes for the susceptibility to the disease we conducted an initial trial of genome-wide analysis.
29 patients with diagnosis of definitive MS and 132 unrelated healthy controls were genotyped using the Affymetrix human 6.0 array. After QC procedures, ancestry determination and a preliminary case-control association study were performed.
We identified significant differences in the European ancestry proportion between MS cases and controls (33.1 vs. 25.56, respectively; p=0.0045). Imputation analysis in the MHC region on chromosome 6 showed a signal with a significant level (p<0.00005) on the HLA-DRB region. Additionally, a preliminary association analysis highlighted the ASF1B as novel candidate gene participating in MS.
Our data suggest that European ancestry is a risk factor to develop MS in Mexican Mestizo population. Conversely, indigenous ancestry of Asian origin seems to confer protection. Further studies with more MS cases are needed to confirm these findings.
多发性硬化症（MS）是一种复杂的免疫介导疾病。有人提出，遗传因素可以解释不同种族患病率的差异。为了了解遗传血统是否是墨西哥患者患MS的潜在风险因素，并确定该疾病易感性的候选基因，我们进行了一项全基因组分析的初步试验。
使用Affymetrix人类6.0芯片对29例确诊为MS的患者和132名无关健康对照进行基因分型。经过质量控制程序后，进行了血统测定和初步的病例对照关联研究。
我们发现MS病例和对照之间欧洲血统比例存在显著差异（分别为33.1和25.56；p = 0.0045）。对6号染色体上的MHC区域进行的插补分析显示，HLA-DRB区域有一个具有显著水平的信号（p < 0.00005）。此外，初步关联分析突出了ASF1B作为参与MS的新候选基因。
我们的数据表明，欧洲血统是墨西哥梅斯蒂索人群患MS的一个风险因素。相反，亚洲血统的本土血统似乎具有保护作用。需要对更多MS病例进行进一步研究以证实这些发现。
