Association of Toll-like receptor polymorphisms with HIV status in North Americans.

Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes TLR2-4 and TLR7-9, but not in TLR1 and TLR6, have been previously evaluated regarding human immunodeficiency virus (HIV) acquisition and disease progression in various populations, most of which were European. In this study, we examined associations between a total of 41 SNPs in 8 TLR genes (TLR1-4, TLR6-9) and HIV status in North American subjects (total n=276 (Caucasian, n=102; African American, n=150; other, n=24)). Stratification of the data by self-identified race revealed that a total of nine SNPs in TLR1, TLR4, TLR6 and TLR8 in Caucasians, and two other SNPs, one each in TLR4 and TLR8, in African Americans were significantly associated with HIV status at P<0.05. Concordant with the odds ratios of these SNPs, significant differences were observed in the SNP allele frequencies between HIV+ and HIV- subjects. Finally, in Caucasians, certain haplotypes of single (TLR1 and TLR4) and heterodimer (TLR2_TLR6) genes may be inferred as 'susceptible' or 'protective'. Our study provides in-depth insight into the associations between TLR variants, particularly TLR1 and TLR6, and HIV status in North Americans, and suggests that these associations may be race specific.

Variation in human ß-defensin genes: new insights from a multi-population study.

Human ß-defensin 2 (hBD-2) and hBD-3, encoded by DEFB4 and DEFB103A, respectively, have shown anti-HIV activity, and both genes exhibit copy number variation (CNV). Although the role of hBD-1, encoded by DEFB1, in HIV-1 infection is less clear, single nucleotide polymorphisms (SNPs) in DEFB1 may influence viral loads and disease progression. We examined the distribution of DEFB1 SNPs and DEFB4/103A CNV, and the relationship between DEFB1 SNPs and DEFB4/103A CNV using samples from two HIV/AIDS cohorts from the United States (n = 150) and five diverse populations from the Coriell Cell Repositories (n = 46). We determined the frequencies of 10 SNPs in DEFB1 using a post-PCR, oligonucleotide ligation detection reaction-fluorescent microsphere assay, and CNV in DEFB4/103A by real-time quantitative PCR. There were noticeable differences in the frequencies of DEFB1 SNP alleles and haplotypes among various racial/ethnic groups. The DEFB4/103A copy numbers varied from 2 to 8 (median, 4), and there was a significant difference between the copy numbers of self-identified whites and blacks in the US cohorts (Mann-Whitney U-test P = 0.04). A significant difference was observed in the distribution of DEFB4/103A CNV among DEFB1 -52G/A and -390T/A genotypes (Kruskal-Wallis P = 0.017 and 0.026, respectively), while not in the distribution of DEFB4/103A CNV among -52G/A_-44C/G_-20G/A diplotypes. These observations provide additional insights for further investigating the complex interplay between ß-defensin genetic polymorphisms and susceptibility to, or the progression or severity of, HIV infection/disease.

Identification of gentian violet concentration that does not stain oral mucosa, possesses anti-candidal activity and is well tolerated.

Gentian violet (GV) is recommended for initial treatment of oral candidiasis in HIV-infected patients in resource-limited settings. Currently GV is not used because of its staining effects. In this study, we investigated the staining capacity of three different concentrations of GV to determine a concentration that does not cause staining. The selected concentration that did not cause staining was evaluated for its physical stability and antifungal activity. Fifteen healthy participants were randomized to rinse twice daily for 14 days with one of three GV concentrations: 0.1%, 0.0085%, or 0.00165%. Oral examination and intra-oral photographs were performed at baseline and at the end of therapy. Participants responded to a questionnaire to assess adverse events. Antifungal activity was evaluated using the Clinical and Laboratory Standard Institute methodology. GV at a concentration of 0.00165% did not stain the oral mucosa and was well tolerated. GV at a concentration of 0.00165% was stable and possessed antifungal activity when stored at certain temperatures for different time periods. Gentian violet solution at the concentration of 0.00165% does not stain the oral mucosa, is stable and possesses potent antifungal activity.

Single-nucleotide polymorphisms and haplotype analysis in beta-defensin genes in different ethnic populations.

Beta-defensins are cationic antimicrobial peptides expressed by epithelial cells and exhibit antibacterial, antifungal, and antiviral properties. The defensins are part of the innate host defense network and may have a significant protective role in the oral cavity and other mucosa. Defects or alteration in expression of the beta-defensins may be associated with susceptibility to infection and mucosal disorders. We examined the occurrence of single-nucleotide polymorphisms (SNPs) in the human beta-defensin genes DEFB1 and DEFB2 encoding human beta-defensin-1 and -2 (hBD-1, hBD-2), respectively, in five ethnic populations and defined haplotypes in these populations. Fifteen SNPs were identified in both DEFB1 and DEFB2. Coding region SNPs were found in very low frequency in both genes. One nonsynonymous DEFB1 SNP, G1654A (Val --> Ile), and one nonsynonymous DEFB2 SNP, T2312A (Leu --> His), were identified. Seven sites in each gene exhibited statistically significant differences in frequency between ethnic groups, with the greatest variation in the promoter and in the 5'-untranslated region of DEFB1. DEFB1 displayed 10 common haplotypes, including one cosmopolitan haplotype. Eight common haplotypes were found in DEFB2, including one cosmopolitan haplotype shared among all five ethnic groups. Our results show that genotypic variability among ethnic groups will need to be addressed when performing associative genetic studies of innate defense mechanisms and susceptibility to disease.