An investigation of susceptibility loci in benign, aggressive and primary progressive multiple sclerosis in Northern Irish population
An investigation of susceptibility loci in benign, aggressive and primary progressive multiple sclerosis in Northern Irish population
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DOI：
10.1177/1352458508099611
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发表时间：
2009-03-01
影响因子：
5.8
通讯作者：
Hawkins, S. A.
中科院分区：
文献类型：
--
作者：
Gray, O. M.;Abdeen, H.;Hawkins, S. A.
目的探讨多发性硬化症(MS)易感基因座在决定北爱尔兰人群疾病预后中的作用。背景欧洲多发性硬化症遗传分析(GAMES)倡议和后续改进分析在北爱尔兰人群中确定了15个候选多发性硬化症易感基因座。我们的目的是调查12个最重要的标记物在疾病结局中的作用。方法将可能或明确MS(Poser标准)的病例分为良性起病(Kurtzke扩展残疾状态评分[EDSS]=6.0×10年)和原发进展型MS。从静脉血中提取DNA，用聚合酶链式反应扩增微卫星标记，用荧光片段分析进行分型。结果两个微卫星标记D3S1278(Chr 3Q13，P<；0.001)和肿瘤坏死因子-α(Chr 6p21，P<；0.001)具有统计学意义。D4S432(Chr 4p16，P=0.001)、D2S347(Chr 2Q14，P=0.003)和D19S903(Chr 19p13，P=0.003)。结论这是首次发现肿瘤坏死因子-α在多发性硬化症疾病预后中的作用，需要进行更大范围的重复研究来评估标志物D4S432、D2S347和D19S903的作用。多发性硬化症2009；15：299-303。Http://msj.sagepub.com
Objective To investigate the possibility that susceptibility loci in multiple sclerosis (MS) have a role in determining the disease outcome in Northern Ireland population.Background The Genetic Analysis of Multiple Sclerosis in Europeans (GAMES) initiative and follow-up refined analysis identified 15 candidate susceptibility loci within the Northern Irish population for MS. We aimed to investigate the 12 most significant markers for their role in disease outcome.Methods Cases with probable or definite MS (Poser criteria) were classified as benign onset (Kurtzke Expanded Disability Status Scale [EDSS] = 6.0 by 10 years), or primary progressive MS. All cases were Caucasian of Northern Irish origin. DNA was extracted from venous blood, microsatellite markers were amplified using polymerase chain reaction and typed using fluorescent fragment analysis. Allele frequencies were compared statistically using a chi-squared test with allowance for multiple comparisons (critical P < 0.0042); significant markers were further analyzed by CLUMP (critical P < 0.0014).Results Two microsatellite markers were significant: D3S1278 (Chr 3q13, P < 0.001) and tumor necrosis factor (TNF)-alpha (Chr 6p21, P < 0.001). A further three markers were significant in our preliminary analysis suggesting a trend toward impact on disease outcome; D4S432 (Chr 4p16, P = 0.001), D2S347 (Chr 2q14, P = 0.003), and D19S903 (Chr 19p13, P = 0.003).Conclusions This is the first study to suggest a role for TNF-alpha in the disease outcome in MS. Larger replication studies need to be performed to assess the role of markers D4S432, D2S347, and D19S903. Multiple Sclerosis 2009; 15: 299-303. http://msj.sagepub.com