β-Defensin 1 haplotype associated with postoperative endophthalmitis.
OBJECTIVE
Endophthalmitis is a rare but sight-threatening complication of intraocular surgery. β-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 β-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.


CONCLUSIONS
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 β-defensin 1 peptide and could therefore reduce the innate ocular immune defence.
Carter
James G
JG
University of Bristol, UK.
West
Stephanie K
SK
Painter
Sally
S
Haynes
Richard J
RJ
Churchill
Amanda J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002387:Cataract Extraction; D023082:Defensins / Q000235:genetics*; D009877:Endophthalmitis / Q000209:etiology* / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications
C478968:Defb1 protein, rat; D023082:Defensins