title: Associations of Toll-Like Receptor and β-Defensin Polymorphisms with Measures of Periodontal Disease (PD) in HIV+ North American Adults: An Exploratory Study.
abstract: Polymorphisms in toll-like receptor (TLR) and β-defensin (DEFB) genes have been recognized as potential genetic factors that can influence susceptibility to and severity of periodontal diseases (PD). However, data regarding associations between these polymorphisms and PD are still scarce in North American populations, and are not available in HIV+ North American populations. In this exploratory study, we analyzed samples from HIV+ adults (n = 115), who received primary HIV care at 3 local outpatient HIV clinics and were monitored for PD status. We genotyped a total of 41 single nucleotide polymorphisms (SNPs) in 8 TLR genes and copy number variation (CNV) in DEFB4/103A. We performed regression analyses for levels of 3 periodontopathogens in subgingival dental plaques (Porphyromonas gingivalis [Pg], Treponema denticola [Td], and Tannerella forsythia [Tf]) and 3 clinical measures of PD (periodontal probing depth [PPD], gingival recession [REC], and bleeding on probing [BOP]). In all subjects combined, 2 SNPs in TLR1 were significantly associated with Td, and one SNP in TLR2 was significantly associated with BOP. One of the 2 SNPs in TLR1 was significantly associated with Td in Caucasians. In addition, another SNP in TLR1 and a SNP in TLR6 were also significantly associated with Td and Pg, respectively, in Caucasians. All 3 periodontopathogen levels were significantly associated with PPD and BOP, but none was associated with REC. Instrumental variable analysis showed that 8 SNPs in 6 TLR genes were significantly associated with the 3 periodontopathogen levels. However, associations between the 3 periodontopathogen levels and PPD or BOP were not driven by associations with these identified SNPs. No association was found between DEFB4/103A CNV and any periodontopathogen level or clinical measure in all samples, Caucasians, or African Americans. Our exploratory study suggests a role of TLR polymorphisms, particularly TLR1 and TLR6 polymorphisms, in PD in HIV+ North Americans.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Mehlotra
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Noemi B
authors.initials: NB
authors.lastname: Hall
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Barne
authors.initials: B
authors.lastname: Willie
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.|Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Department of Biological Sciences, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
authors.affiliation: Department of Pediatric and Community Dentistry, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio, United States of America.
authors.forename: Lance T
authors.initials: LT
authors.lastname: Vernon
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009656:North America; D010510:Periodontal Diseases / Q000150:complications / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016966:Porphyromonas gingivalis / Q000302:isolation & purification; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000070436:Tannerella forsythia / Q000302:isolation & purification; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051216:Toll-Like Receptor 6 / Q000235:genetics*; D048373:Treponema denticola / Q000302:isolation & purification; D044465:White People / Q000235:genetics; D023083:beta-Defensins / Q000235:genetics*
chemical_list: C106641:DEFB4A protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D023083:beta-Defensins; D004247:DNA