Genome-wide SNP-based linkage analysis of tuberculosis in Thais
Genome-wide SNP-based linkage analysis of tuberculosis in Thais
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DOI：
10.1038/gene.2008.81
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发表时间：
2009-01-01
影响因子：
5
通讯作者：
Keicho, N.
中科院分区：
文献类型：
--
作者：
Mahasirimongkol, S.;Yanai, H.;Keicho, N.
结核病是一种潜在的致命传染病，每年影响全世界数百万人。感染结核病后的人体保护性免疫尚未明确定义。为了深入了解宿主遗传因素，使用基于高通量微阵列的单核苷酸多态性（SNP）基因分型平台进行非参数连锁分析，GeneChip阵列包含59 860个双等位基因标记，在93个泰国多兄弟姐妹家庭中，195名结核病患者。基因分型显示染色体5q上的一个区域显示与结核病连锁的证据（Z（lr）统计量3.01，比值对数（LOD）得分2.29，经验P值=0.0005），并且通过使用结核病发病时的最小年龄作为协变量的有序子集分析，染色体17 p和20 p上的两个候选区域（最大LOD评分分别为2.57和3.33，排列P值分别为0.0187和0.0183）。这些结果意味着亚洲人群中结核病遗传危险因素的新证据。这些有序子集结果的重要性支持了一个临床病理学概念，即年轻和老年结核病患者之间疾病的免疫损伤不同。来自特定种族的连锁信息可能为鉴定易感基因提供独特的候选区域，并进一步帮助阐明结核病的免疫发病机制。
Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics 3.01, logarithm of odds (LOD) score 2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score = 2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.