Immune defense single nucleotide polymorphisms and recruitment strategies associated with contact lens keratitis.

PURPOSE: To determine the association of single nucleotide polymorphisms (SNPs) of defensin 1B and toll-like receptor 4 with contact lens keratitis susceptibility and severity, and to understand the factors that influence study participation.

DESIGN

Retrospective, case-control study.

PARTICIPANTS

Ninety cases of keratitis and 185 controls recruited from studies conducted at Moorfields Eye Hospital and throughout Australia from 2003 to 2005 were analyzed for genetic associations. The reasons for participation of a subset of 146 participants from 1 site were also investigated.

METHODS

Buccal swab samples were collected on Whatman FTA cards and mailed by post for analysis. DEFB1 (rs1799946, -52, rs1800972, -44, and rs11362, -20) and TLR4 (rs4986790, D299G) SNPs were screened by pyrosequencing and analyzed using a regression model for susceptibility (sterile, microbial keratitis [MK], controls) and severity. Study participation was investigated for age, gender, condition, and phone follow-up also using regression analysis.

MAIN OUTCOME MEASURES: Relative risk of developing contact lens-related keratitis and more severe forms of the disease based on genetic profiles.

RESULTS

Carriers of risk alleles of DEFB1 -52 and -20 showed a trend toward increased susceptibility to keratitis (-52: odds ratio [OR], 1.45; 95% confidence interval [CI], 0.99-2.11; P = 0.051; -20: OR, 1.37; 95% CI, 0.95-1.98; P = 0.088). A DEFB1 promoter haplotype (G-G-A) had a tendency toward decreased susceptibility of MK (OR, 0.68; 95% CI, 0.45-1.03; P = 0.062) and reduced severity (OR, 0.56; 95% CI, 0.30-1.07; P = 0.066). The TLR4 D299G was not associated with type and severity of keratitis. Older age (OR, 1.07; 95% CI, 1.05-1.08) and follow-up phone call (OR, 2.0; 95% CI, 1.2-3.5) were independent predictors of study participation.

CONCLUSIONS

Genetic variation in DEFB1 that may lead to decreased protein expression of hBD-1 exhibits a tendency toward increased susceptibility and severity of contact lens-related keratitis. Investigation of these and other hBD genes that play important roles in animal models in a larger sample size is warranted. The approach of requesting samples from retrospective case series was generally feasible, although significant resources, including repeat phone calls, are required. More targeted strategies to recruit younger individuals to participate in genetic studies may be useful.