Lin Marie, Tseng Hsiang-Kuang, Trejaut Jean A, Lee Hui-Lin, Loo Jun-Hun, Chu Chen-Chung, Chen Pei-Jan, Su Ying-Wen, Lim Ken Hong, Tsai Zen-Uong, Lin Ruey-Yi, Lin Ruey-Shiung, Huang Chun-Hsiung
Transfusion Medicine Laboratory, Mackay Memorial Hospital, Taipei, Taiwan.
BMC Med Genet. 2003 Sep 12;4:9. doi: 10.1186/1471-2350-4-9.
The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection.
HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis.
Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279).
Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.
人类白细胞抗原（HLA）系统被广泛用作寻找传染病和自身免疫性疾病病因的一种策略。在台湾严重急性呼吸综合征（SARS）疫情期间，许多医护人员被感染。为了建立针对高危人群的筛查项目，研究了病例组和对照组中HLAⅠ类和Ⅱ类等位基因的分布情况，以确定是否存在与SARS冠状病毒感染的遗传易感性或抗性相关的关联。
对37例疑似SARS病例、28例后来被排除为疑似SARS的发热患者以及101名暴露于或可能暴露于SARS冠状病毒的未感染医护人员进行了PCR-SSOP HLAⅠ类和Ⅱ类等位基因分型。另外还使用了190名正常健康的无亲缘关系的台湾人作为对照组进行分析。
采用Woolf和Haldane比值比（OR）以及双尾Fisher精确检验得到的校正P值（Pc）来显示HLAⅠ类或Ⅱ类等位基因对冠状病毒感染的易感性。首先，在分析感染的SARS患者和高危医护人员组时，HLA-B4601（OR = 2.08，P = 0.04，Pc = 无统计学意义）和HLA-B5401（OR = 5.44，P = 0.02，Pc = 无统计学意义）似乎是最可能有利于SARS冠状病毒感染的因素。从感染的“疑似SARS”患者组中仅选择“重症病例”患者组并将其与高危医护人员组进行比较后，发现SARS的严重程度与HLA-B*4601显著相关（P = 0.0008或Pc = 0.0279）。
南亚人群基因相关的人口密集地区似乎更容易受到SARS感染传播的影响。直到最近，在与台湾普通人群基因不同、没有HLA-B4601且HLA-B1301频率较高的台湾原住民中，没有报告疑似SARS患者。虽然在“疑似SARS感染”患者组中观察到HLA-B4601等位基因频率增加，但在“重症病例”患者组中该等位基因进一步显著增加。这些结果似乎表明HLA-B4601与亚洲人群中SARS感染的严重程度有关。需要进行独立研究来验证这些结果。
