The role of genetic polymorphisms in the development of clinical forms of human herpesvirus 6 infection in children
The objective. To assess the prognostic significance of single nucleotide polymorphisms (SNP) of human genes in the development of clinical forms of infection caused by human herpesvirus type 6 (HHV-6). Patients and methods. We examined 77 children aged 1 to 14 years. The treatment group consisted of 40 children admitted to an infectious unit with clinical signs of infection caused by HHV-6, the control group comprised 37 clinically healthy children. Criteria of inclusion were detection of HHV-6 DNA in blood serum in the absence of DNA of other herpesviruses. Single nucleotide polymorphisms (SNP) of toll-like receptors 3 and 9 (TLR9: -1486 T>C, TLR3 908T>C,) genes, cryopyrin (NLRP3 2107C>A), low-affinity IgG Fc region receptor IIa (FCGR2A His166Arg), interferon-induced MX1 protein (Mх1 G-88T, Mх1 C-123A), interferon-induced transmembrane protein 3 (IFITM3 rs12252), C-C chemokine receptor 5 (CCR5 -2554G>T, CCR5 -2459A>G) and its variant «delta 32 mutation» with a 32 base pair deletion (CCR5: delta32) were investigated. Results. Children under 4 years of age with clinical signs of HHV-6 infection by 4-5 times more often are carriers of a heterozygous CA polymorphism in Mx1: -123 C>A and a GT polymorphism in Мх1: -88G>T as compared with healthy children (relative risk ratios RR = 4.38 and RR = 5.0, respectively; р < 0.05). In investigating the CCR5 gene polymorphisms at -2554 a substitution of cytosine for thymine (CCR5 -2554G>T) in patients with clinical signs of HHV-6 infection in the age group of 4-year-olds and older, significantly more often the GG genotype was found (RR = 1.89; р < 0.05). Conclusion. Development of clinical forms of HHV-6 infection in children is related to genetic polymorphisms of antiviral proteins and the С-С chemokine receptor 5. In children under 4 years the development of clinical forms of infection is promoted by the presence in a patient of the CT variant of Mx1 polymorphism: -123 C>A and the GT variant of Mx1 polymorphism: -88G>T, for children older than 4 years - the GG variant of the CCR5 polymorphism: -2554 G>T.