Abstract

Background

Chikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya.

Methods

To test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays.

Results

After adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively).

Conclusion

This study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.

中文翻译：

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尼加拉瓜 DC-SIGN、Toll 样受体 3、肿瘤坏死因子 α 基因和 Lewis 阴性表型与基孔肯雅热感染和疾病的遗传多态性的关联

摘要

背景

基孔肯雅热感染的范围从亚临床感染到使人衰弱的关节痛和慢性炎症性风湿病。肿瘤坏死因子 (TNF) α、DC-SIGN（树突状细胞特异性细胞间粘附分子 3-抓取非整合素）、Toll 样受体 (TLR) 3 和血型直接或间接地与基孔肯雅热的易感性和发病机制有关.

方法

为了检验编码这些分子的基因的多态性决定基孔肯雅热感染的临床结果的假设，在尼加拉瓜莱昂进行了一项回顾性病例对照研究。该研究包括 132 名病例患者和 132 名对照，年龄、性别和社区相匹配。病例患者有基孔肯雅热的临床症状，经聚合酶链反应确诊。对照是未报告突然出现临床基孔肯雅热样症状的个体。多态性通过 TaqMan 单核苷酸多态性基因分型分析进行鉴定。

结果

在调整社会人口学风险因素后，基孔肯雅热病与 DC-SIGN 和 TLR3 基因的多态性（优势比分别为 5.2 和 3.3）以及 TNF-α 与持续性关节疼痛减轻（0.24）相关。持续性关节疼痛也与年龄、女性和其他合并症有关。最有趣的是，Lewis 阴性表型与有症状的基孔肯雅热和免疫球蛋白 G 血清阳性密切相关（比值比分别为 2.7 和 3.3）。

结论

该研究确定了 DC-SIGN、TLR3 和 TNF-α 基因的多态性以及路易斯阴性表型是基孔肯雅热感染和疾病进展的危险因素。