HLA-DRB1*allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients
HLA-DRB1*allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients
复制标题
DOI：
10.3892/mmr_00000204
复制
发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Donadi, Eduardo Antonio
中科院分区：
文献类型：
--
作者：
Kaimen-Maciel, Damacio Ramon;Vissoci Reiche, Edna Maria;Donadi, Eduardo Antonio
多发性硬化症（MS）是一种慢性自身免疫性中枢神经系统脱髓鞘疾病，可导致年轻人的神经系统疾病。以前在不同人群中的研究强调了HLA-DRB 1 *1.5等位基因和MS之间的关联。本研究调查了来自巴西南部隆德里纳的巴西高加索人群样本中HLA-DRB 1 *15和其他HLA-DRB 1等位基因与MS之间的关联。应用聚合酶链反应（PCR）技术，对119例MS患者和305例健康献血员的HLA-DRB 1等位基因进行分析。在MS患者中，89例（75.0%）表现为复发缓解型MS，24例（20.0%）表现为继发性进展型MS，6例（5.0%）表现为原发性进展型MS。在MS巴西患者中观察到的HLA-DRB 1 *15等位基因频率与在全球人群中进行的先前研究中报告的结果相似。然而，结果显示MS患者中HLA-DRB 1 *15等位基因的频率高于对照组，相对频率分别为0.1050（10.50%）和0.0443（4.4%）（OR=2.53; 95%CI 1.43-4.46; p=0.0009）。还检测到保护等位基因。与对照组相比，MS患者中HLA-DRB 1 *11等位基因的频率降低，相对频率分别为0.1345（13.4%）和0.1869（18.7%）（OR=0.67; 95%CI 0.44-1.03; p=0.0692）。结果表明，HLA-DRB 1 *15等位基因的杂合性与MS呈正相关（p=0.0079），可作为MS易感性的遗传标记。HLA-DRB 1 *11等位基因纯合性和MS之间的负相关性也得到了验证（p=0.0418）;该等位基因可被认为是巴西人群中MS抗性的遗传标记。
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system that causes neurological disorders in young adults. Previous studies in various populations highlighted an association between the HLA-DRB1*1.5 allele and MS. This study investigated the association between HLA-DRB1*15 and other HLA-DRB1 alleles and MS in a Brazilian Caucasian population sample from Londrina, Southern Brazil. HLA-DRB1 alleles were analyzed by polymerase chain reaction with specific sequence oligonucleotide primers in 119 MS patients and in 305 healthy blood donors as a control. Among the MS patients, 89 (75.0%) presented with relapsing remitting MS, 24 (20.0%) with secondary progressive MS and 6 (5.0%) with primary progressive MS. The frequency of the HLA-DRB1*15 allele observed in the MS Brazilian patients was similar to findings reported in previous studies carried out in populations worldwide. However, the results showed a higher frequency of the HLA-DRB1*15 allele in the MS patients compared to the controls, with a relative frequency of 0.1050 (10.50%) and 0.0443 (4.4%), respectively (OR=2.53; 95% CI 1.43-4.46; p=0.0009). A protector allele was also detected. The frequency of the HLA-DRB1*11 allele was reduced in the MS patients compared to the controls, with a relative frequency of 0.1345 (13.4%) and 0.1869 (18.7%), respectively (OR=0.67; 95% CI 0.44-1.03; p=0.0692). The results demonstrated that the HLA-DRB1*15 allele in heterozygosity is positively associated with MS (p=0.0079), and may be considered a genetic marker of susceptibility to the disease. A negative association between the HLA-DRB1*11 allele in homozygosity and MS was also verified (p=0.0418); this allele may be considered a genetic marker of resistance to MS in the Brazilian population.