Genetic variations in human beta defensin genes and their relationship to oral health and disease.

摘要

Beta-defensins are cationic antimicrobial peptides expressed by epithelial cells and exhibit anti-bacterial, anti-fungal and anti-viral 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. The study 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. Previous studies show human beta-defensin-1 (hBD-1) is constitutively expressed in oral epithelial cells, but that expression varies between individuals. These results may indicate genetic variations in the DEFB1 gene encoding hBD-1 may be associated with susceptibility to oral infection. Oral Candida infection is a major complication experienced by immunocompromised patients and patients on various chemotherapeutic regimens, it is also a complication associated with diabetes. Oral Candida carriage status and the presence of 6 single nucleotide polymorphisms in the DEFB1 gene encoding hBD-1 were evaluated in type 1 diabetic patients (n = 43), non-diabetics (n = 50), and HIV+/AIDs (n = 46). High throughput SNP analysis methods were developed and applied to determine SNP frequency and genotype. This investigation demonstrated a SNP in the DEFB1 gene encoding the antimicrobial peptide, hBD-1, (-44 C → G) has a statistically significant association with decreased Candida carriage in both type1 insulin dependent diabetics and non-diabetic subjects. The antifungal efficacy of three beta-defensins (hBD-1, hBD-2, and hBD-3) was assessed by radial diffusion assay methods to determine relative fungicidal activity. hBD-1 did not exhibit any antifungal activity. hBD-2 and hBD-3 exhibited measurable MIC activity towards different Candida isolates. These results suggest hBD-1 may be a genetic marker for Candida carriage and not a direct innate antifungal agent.