TY  - JOUR
AB  - Toll-like receptors (TLRs) play a critical role in initiating an immune response to infections. In this study, we examined whether single nucleotide polymorphisms (SNPs) in TLR pathway genes are associated with pulmonary tuberculosis (PTB) in a Moldavian population. Thirty-four SNPs in genes associated with the TLR pathway and two SNPs in ASAP1 gene identified by GWAS were selected for genotyping in 272 patients and 251 community-matched healthy controls. Twenty-nine SNPs passed quality control and were statistically evaluated. SNPs TLR9 rs352139, TLR2 rs3804099 and MYD88 rs4988453 were associated with PTB in females (OR = 0.49, p = 0.0009; OR = 0.51, p = 0.0008; OR = 0.33, p = 0.027; here and below log-additive model with minor alleles assumed as effect associated alleles), while SNP TLR8 rs3764880 showed a significant association in males (OR = 0.44, p = 0.0087). Furthermore, SNPs TLR9 rs352139 and TLR8 rs3764880 were associated with PTB in the late-onset ( >= 39-year-old) patient group (OR = 0.60, p = 0.0029 and OR = 0.70, p = 0.021, respectively) and SNPs TLR2 rs3804099, TLR4 rs4986790 and TLR4 rs1927906 in the early-onset (<= 38-year-old) group (OR = 0.53, p = 0.0012; OR = 3.45, p = 0.013; OR = 2.31, p = 0.044, respectively). After correction for multiple testing, only SNPs TLR9 rs352139 and TLR2 rs3804099 in the female group and SNP TLR2 rs3804099 in the early-onset group remained significant. In summary, we show an association of SNP TLR8 rs3764880 with PTB in the Moldavian male population, providing support to previous studies conducted on other populations. Polymorphisms rs3804099 (TLR2) and rs352139 (TLR9) may also be associated with PTB risk in the Moldavian population but their effect is less consistent across different studies. Additional large-scale association studies along with functional tests are required to dissect the relevance of these associations.
AU  - Varzari, A.*
AU  - Deyneko, I.V.*
AU  - Vladei, I.*
AU  - Grallert, H.
AU  - Schieck, M.*
AU  - Tudor, E.*
AU  - Illig, T.*
C1  - 54936
C2  - 45984
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - 84-90
TI  - Genetic variation in TLR pathway and the risk of pulmonary tuberculosis in a Moldavian population.
JO  - Infect. Genet. Evol.
VL  - 68
PB  - Elsevier Science Bv
PY  - 2019
SN  - 1567-1348
ER  - 

TY  - JOUR
AB  - Norovirus has become an important cause for infectious gastroenteritis. Particularly genotype II.4 (GII.4) has been shown to spread rapidly and causes worldwide pandemics. Emerging new strains evade population immunity and lead to high norovirus prevalence. Chronic infections have been described recently and will become more prevalent with increasing numbers of immunocompromized patients. Here, we studied norovirus evolution in three chronically infected patients, two genotypes II.4 and one II.7. A 719 and 757 nt region was analyzed for GII.4 and GII.7, respectively. This covers the entire hypervariable P2 domain of the VP1 capsid gene. Genetic variability at given and between different time points was assessed. Evolutionary adaptation was analyzed by Bayesian sampling of genealogies. This analysis clearly demonstrated positive selection rather than incidental drift for all three strains. The GII.7 and one GII.4 strain accumulated on average 5-9 mutations per 100 days, most of them non-synonymous. This is a much higher evolutionary rate than observed for noroviruses on a global level. Our data demonstrate that norovirus quasispecies are positively selected in chronically infected patients. The numbers of intraindividual amino acid mutations acquired in the capsid gene are similar to those separating consecutive GII.4 epidemic strains. Evolution in a given, chronically infected individual may thus generate novel genotypes at risk to expedite global evolution particularly for slowly evolving genotypes, as GII.7.
AU  - Hoffmann, D.*
AU  - Hutzenthaler, M.*
AU  - Seebach, J.*
AU  - Panning, M.*
AU  - Umgelter, A.*
AU  - Menzel, H.*
AU  - Protzer, U.
AU  - Metzler, D.*
C1  - 7512
C2  - 29772
SP  - 461-466
TI  - Norovirus GII.4 and GII.7 capsid sequences undergo positive selection in chronically infected patients.
JO  - Infect. Genet. Evol.
VL  - 12
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 1567-1348
ER  -