Alagarasu K, Bachal R V, Tillu H, Mulay A P, Kakade M B, Shah P S, Cecilia D
Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India.
Dengue Group, National Institute of Virology, 20 A, Dr Ambedkar Road, Pune 411001, Maharashtra, India.
Cytokine. 2015 Jul;74(1):130-6. doi: 10.1016/j.cyto.2015.03.021. Epub 2015 Apr 16.
Pro-inflammatory and anti-inflammatory cytokines have been shown to play an important role in dengue disease pathogenesis. In the present study, to find out whether single nucleotide polymorphisms (SNPs) in the pro-inflammatory and anti-inflammatory cytokine genes are associated with dengue disease severity, SNPs in TNF, IFNG, IL1B, IL8, IL0, IL17A and IL17F genes were investigated using polymerase chain reaction based methods in 132 dengue (DEN) cases [87 dengue fever (DF), 45 dengue hemorrhagic fever (DHF) cases] and 108 apparently healthy controls (HC) from Pune, Maharashtra, western India. Under recessive genetic model (C/C vs. T/T+T/C), the TNF rs1799964 C/C genotype was significantly associated with DEN [P=0.014, OR with 95% CI 3.07 (1.18-7.98)]. Frequency of T/C genotype of IL17F rs763780 was significantly lower in DEN group as compared to HC [P=0.033, OR with 95% CI 0.43 (0.19-0.95)]. Under overdominant genetic model (A/T vs. A/A+T/T), IL8 rs4973 A/T genotype was negatively associated with DHF compared to HCs [p=0.029, OR with 95% CI 0.43 (0.20-0.93)]. Under overdominant genetic model, A/G genotype of IL10 rs1800871 was significantly negatively associated with DHF compared to DF cases [p=0.014, OR with 95% CI 0.35 (0.15-0.84)]. Significantly higher frequency of the combined genotype IL10 A/A-IFNG A/T and lower frequency of the combined genotypes IL10 A/G-IL1B A/A, IL10 A/G-IL8 A/T and IL10 A/G-IL17F T/T were observed in DHF cases compared to DF. The results suggest that heterozygous genotypes of IL8 rs4973 and IL10 rs1800871 are associated with reduced risk of DHF. Combinations of IL10 rs1800871 and pro-inflammatory cytokine genotypes influence the risk of DHF.
促炎细胞因子和抗炎细胞因子已被证明在登革热疾病发病机制中起重要作用。在本研究中，为了探究促炎和抗炎细胞因子基因中的单核苷酸多态性（SNP）是否与登革热疾病严重程度相关，我们采用基于聚合酶链反应的方法，对来自印度西部马哈拉施特拉邦浦那的132例登革热（DEN）病例[87例登革热发热（DF）、45例登革出血热（DHF）病例]和108例健康对照（HC）的肿瘤坏死因子（TNF）、干扰素γ（IFNG）、白细胞介素1β（IL1B）、白细胞介素8（IL8）、白细胞介素10（IL10）、白细胞介素17A（IL17A）和白细胞介素17F（IL17F）基因中的SNP进行了研究。在隐性遗传模型（C/C与T/T+T/C）下，TNF rs1799964 C/C基因型与DEN显著相关[P=0.014，优势比（OR）及95%置信区间为3.07（1.18 - 7.98）]。与HC相比，DEN组中IL17F rs763780的T/C基因型频率显著降低[P=0.033，OR及95%置信区间为0.43（0.19 - 0.95）]。在共显性遗传模型（A/T与A/A+T/T）下，与HC相比，IL8 rs4973 A/T基因型与DHF呈负相关[p=0.029，OR及95%置信区间为0.43（0.20 - 0.93）]。在共显性遗传模型下，与DF病例相比，IL10 rs1800871的A/G基因型与DHF显著负相关[p=0.014，OR及95%置信区间为0.35（0.15 - 0.84）]。与DF相比，DHF病例中IL10 A/A - IFNG A/T联合基因型的频率显著更高，而IL10 A/G - IL1B A/A、IL10 A/G - IL8 A/T和IL10 A/G - IL17F T/T联合基因型的频率更低。结果表明，IL8 rs4973和IL10 rs1800871的杂合基因型与DHF风险降低相关。IL10 rs1800871与促炎细胞因子基因型的组合会影响DHF风险。
