TLR9 -1486T/C and 2848C/T SNPs Are Associated with Human Cytomegalovirus Infection in Infants.
Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni's correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease.
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Edyta
E
Paradowska
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Agnieszka
A
Jabłońska
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Mirosława
M
Studzińska
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Katarzyna
K
Skowrońska
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Patrycja
P
Suski
Department of Pediatrics, Immunology, and Nephrology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Małgorzata
M
Wiśniewska-Ligier
3rd Department of Pediatrics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Teresa
T
Woźniakowska-Gęsicka
Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Dorota
D
Nowakowska
Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.|Scientific Laboratory of the Center of Medical Laboratory Diagnostics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Zuzanna
Z
Gaj
2nd Department of Obstetrics and Gynecology, Warsaw Medical University, Warsaw, Poland.
Jan
J
Wilczyński
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Zbigniew J
ZJ
Leśnikowski
D000483:Alleles; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics*
D004279:DNA, Viral; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9