Ding Shu-Jun, Zhang Yi, Zhang Xiao-Mei, Jiang Xiao-Lin, Pang Bo, Song Yong-Hong, Wang Jian-Xing, Pei Yao-Wen, Zhu Chuan-Fu, Wang Xian-Jun, Yu Xue-Jie
Department of Viral Infectious Diseases Control and Prevention, Shandong Provincial Key Laboratory of Communicable Disease Control and Prevention, Shandong Center for Disease Control and Prevention, Jinan, Shandong Province, China.
HLA Lab,Blood Center of Shandong Province, Jinan, Shandong Province, China.
PLoS Negl Trop Dis. 2016 Oct 19;10(10):e0005076. doi: 10.1371/journal.pntd.0005076. eCollection 2016 Oct.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.
A total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf's method.
A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A30 and B13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A30 and B13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A30-B13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96) without significance(Pc>0.05). A30-B13-DRB107 and A02-B15-DRB104 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).
The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A30, HLA-B13 and Haplotype A30-B13, although the associations were not statistically significant. A30-B13-DRB107 had negative correlation with the occurrence of SFTS; in contrast, haplotype A02-B15-DRB104 was positively correlated with SFTS.
严重发热伴血小板减少综合征(SFTS)是一种由蜱传布尼亚病毒(SFTSV)引起的在东亚国家新出现的出血热。人类白细胞抗原(HLA)在抵抗和易感染SFTSV方面的作用尚不清楚。我们研究了HLA基因座A、B和DRB1等位基因与SFTS发生之间的相关性。
采用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)技术,对来自山东省的84例确诊SFTS患者(患者组)和501例无血缘关系的非SFTS患者(健康个体作为对照组)进行HLA-A、B和DRB1基因座的基因分型。计算等位基因频率,并采用χ2检验或Fisher精确检验进行比较。使用Bonferroni校正计算校正P值。采用Woolf法计算比值比(OR)和95%置信区间(CI)。
患者组共鉴定出11个HLA-A、23个HLA-B和12个HLA-DRB1等位基因,而对照组检测到15个HLA-A、30个HLA-B和13个HLA-DRB1等位基因。SFTS患者组中A30和B13的频率低于对照组(P = 0.0341和0.0085,Pc = 0.5115和0.252)。SFTS患者组中A30和B13的OR分别为0.54和0.49。患者组中两位点单倍型A30-B13的频率低于对照组(5.59%对12.27%,P = 0.037,OR = 0.41,95%CI = 0.18 - 0.96),无统计学意义(Pc>0.05)。A30-B13-DRB107和A02-B15-DRB104分别与SFTS抵抗和易感性密切相关(Pc = 0.0412和0.0001,OR = 0.43和5.07)。
宿主HLA I类多态性可能在SFTS的发生中起重要作用。观察到HLA-A30、HLA-B13和单倍型A30-B13存在负相关,尽管这些关联无统计学意义。A30-B13-DRB107与SFTS的发生呈负相关;相反,单倍型A02-B15-DRB104与SFTS呈正相关。