title: Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents.
abstract: Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age, especially among women with HIV-1 infection. Several bacterial products including lipopolysaccharides (LPS), lipoteichoic acids (LTA), and peptidoglycans (PGN) are stimulatory ligands for Toll-like receptors (TLRs), and recent evidence indicates the important role of variation in TLR genes for permitting overgrowth of gram negative and BV-type flora. We assessed whether genetic polymorphisms in five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR9) could be determinants of differential host immune responses to BV in 159 HIV-1-positive African American adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. BV was assessed biannually and diagnosed either by a Nugent score of at least 7 of 10, or using the Amsel criteria. Cox-proportional hazards regression models, adjusted for concurrent Chlamydia and Gonorrhea infections, douching, and absolute CD4 cell count, were used to identify host genetic factors associated with BV. Two SNPs were associated with BV as diagnosed by the Nugent score and the combined criteria: a minor allele G of rs4986790 (frequency=0.07), which encodes a His to Tyr substitution in TLR4 (HR=1.47, 95% CI 1.15-1.87) and rs187084 (frequency=0.24) on TLR9. The minor allele of rs1898830 (frequency=0.13) was associated with an increased hazard of BV defined by the Amsel criteria (HR=1.86, 95% CI 1.17-2.95). Further studies are warranted to confirm the associations of TLR gene variants and also to understand the underlying pathways and immunogenetic correlates in the context of HIV-1 infection.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294-0022, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Royse
authors.forename: Mirjam-Colette
authors.initials: MC
authors.lastname: Kempf
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Sadeep
authors.initials: S
authors.lastname: Shrestha
mesh_terms: D000293:Adolescent; D001741:Black or African American; D002690:Chlamydia Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006069:Gonorrhea / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*; D016585:Vaginosis, Bacterial / Q000150:complications / Q000235:genetics* / Q000276:immunology
chemical_list: C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors