Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Ratchawithi Road, Bangkok, 10400, Thailand.
Laboratory of Human Genome Diversity, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
BMC Infect Dis. 2020 Dec 11;20(1):948. doi: 10.1186/s12879-020-05636-w.
Dengue patients develop different disease severity ranging from mild (dengue fever [DF]) to severe forms (dengue hemorrhagic fever [DHF] and the fatal dengue shock syndrome [DSS]). Host genetics are considered to be one factor responsible for the severity of dengue outcomes. To identify genes associated with dengue severity that have not been studied yet, we performed genetic association analyses of interferon lambda 3 (IFNL3), CD27, and human leukocyte antigen-DPB1 (HLA-DPB1) genes in Thai dengue patients.
A case-control association study was performed in 877 children (age ≤ 15 years) with dengue infection (DF, n = 386; DHF, n = 416; DSS, n = 75). A candidate single nucleotide polymorphism of each of IFNL3, CD27, and HLA-DPB1 was selected to be analyzed. Genotyping was performed by TaqMan real-time PCR assay, and the association with dengue severity was examined.
The rs9277534 variant of HLA-DPB1 was weakly associated with DHF. The genotype GG and G allele conferred protection against DHF (p = 0.04, odds ratio 0.74 for GG genotype, p = 0.03, odds ratio 0.79 for G allele). The association became borderline significant after adjusting for confounders (p = 0.05, odds ratio 0.82). No association was detected for IFNL3 or CD27.
The present study demonstrated the weak association of the rs9277534 variant of HLA-DPB1 with protection against DHF. This variant is in the 3' untranslated region and affects HLA-DPB1 surface protein expression. Our finding suggests that HLA-DPB1 may be involved in DHF pathogenesis.
登革热患者的疾病严重程度不同，从轻症（登革热[DF]）到重症（登革出血热[DHF]和致命的登革休克综合征[DSS]）不等。宿主遗传学被认为是导致登革热结局严重程度的一个因素。为了确定尚未研究过与登革热严重程度相关的基因，我们对泰国登革热患者的干扰素 lambda 3（IFNL3）、CD27 和人类白细胞抗原-DPB1（HLA-DPB1）基因进行了遗传关联分析。
对 877 名年龄≤15 岁的登革热感染患儿（DF 患者 386 名，DHF 患者 416 名，DSS 患者 75 名）进行病例对照关联研究。选择每个 IFNL3、CD27 和 HLA-DPB1 的候选单核苷酸多态性进行分析。通过 TaqMan 实时 PCR 检测进行基因分型，并检测与登革热严重程度的关联。
HLA-DPB1 的 rs9277534 变体与 DHF 呈弱相关。GG 基因型和 G 等位基因可预防 DHF（p=0.04，GG 基因型的优势比为 0.74，p=0.03，G 等位基因的优势比为 0.79）。调整混杂因素后，相关性具有统计学意义（p=0.05，优势比为 0.82）。IFNL3 或 CD27 未检测到相关性。
本研究表明，HLA-DPB1 的 rs9277534 变体与 DHF 的保护呈弱相关。该变体位于 3'非翻译区，影响 HLA-DPB1 表面蛋白表达。我们的发现表明 HLA-DPB1 可能参与 DHF 的发病机制。
