β-Defensin 1 haplotype associated with postoperative endophthalmitis

Purpose:

Endophthalmitis is a rare but sight-threatening complication of intraocular surgery. beta-Defensins are antimicrobial peptides that appear to be important components of the ocular immune response. We propose that variation in defensin genes may alter susceptibility to endophthalmitis.

Methods:

Post-cataract endophthalmitis patients (n = 28) and post-cataract controls (n = 75) were recruited and DNA samples extracted. The beta-defensin 1 gene (DEFB1) was screened for single-nucleotide polymorphisms (SNPs) using bidirectional sequencing. Case-control statistical assessment was undertaken for both the individual polymorphic loci observed and combined haplotypes using PHASE software.

Results:

We identified 19 SNPs and observed strong linkage disequilibrium within the gene. We found that the three-SNP haplotype -688C/-44C/-20A was associated strongly with endophthalmitis [odds ratio (OR) = 8.88 (1.74, 45.42), corrected p = 0.0095]. Furthermore, we uncovered several trends, including increased prevalence of the -44CC genotype in the endophthalmitis group.

Conclusion:

We have shown previously that the -44CC SNP genotype was present in a single case of bilateral endophthalmitis. In this study, we found this genotype to be more common in the endophthalmitis group and a mini-haplotype including this SNP was associated strongly with endophthalmitis. There is functional evidence that this genetic profile decreases transcription of the beta-defensin 1 peptide and could therefore reduce the innate ocular immune defence.