Cross-sectional analysis of Toll-like receptor variants and bacterial vaginosis in African-American women with pelvic inflammatory disease.
OBJECTIVE
Bacterial vaginosis (BV) is a common condition associated with serious complications including pelvic inflammatory disease (PID). However, the pathogenesis of BV is poorly understood. Toll-like receptors (TLR) are responsible for microbial recognition and elimination through inflammatory responses. TLR variants have been implicated in infectious and inflammatory diseases and may be involved in BV pathogenesis. We conducted a cross-sectional study to determine if TLR variants are associated with BV.


METHODS
Logistic regression was used to test associations between 14 variants assayed in 6 genes (TLR1, TLR2, TLR4, TLR6, TIRAP and MyD88) and BV/intermediate flora among 192 African-American women with clinical PID from the PID Evaluation and Clinical Health (PEACH) Study. Additionally, we examined associations between variants and endometrial BV-associated anaerobes. To account for multiple comparisons a permutated p<0.003 was used to determine statistical significance.


RESULTS
African-American women with PID carrying the AA genotype for TLR2 SNP rs1898830 had a threefold increased rate of BV/intermediate flora (OR 2.9, 95% CI 1.2 to 7.3). This was not significant after accounting for multiple comparisons (p=0.0201). TLR2 variants rs1898830, rs11938228 and rs3804099 were associated with increased endometrial anaerobic gram-negative rods (p=0.0107, p=0.0076 p=0.0121), anaerobic non-pigmented Gram-negative rods (p=0.0231, p=0.0083, p=0.0044), and anaerobic Gram-positive cocci (p=0.0596, p=0.0640, p=0.1459).


CONCLUSIONS
Among African-American women with PID, we observed trends between TLR2 variants, BV/intermediate flora, and BV-associated microbes. This provides some insight into BV pathogenesis. As not all BV-associated microbes may lead to pathology, future studies should focus on associations between TLR variants and individual BV-associated microbes.
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Brandie D
BD
Taylor
Department of Pediatrics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.
Toni
T
Darville
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Robert E
RE
Ferrell
University of Texas School of Public Health, Houston, Texas, USA.
Roberta B
RB
Ness
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Sheryl F
SF
Kelsey
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Catherine L
CL
Haggerty
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008562:Membrane Glycoproteins / Q000235:genetics*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D000292:Pelvic Inflammatory Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D051194:Toll-Like Receptor 1 / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051216:Toll-Like Receptor 6 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D014621:Vagina / Q000382:microbiology*; D016585:Vaginosis, Bacterial / Q000235:genetics*; D055815:Young Adult
C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors
Bacterial Vaginosis; Epidemiology (General); Pelvic Inflammatory Disease