Evaluation of Possible Relationship Between COL4A4 Gene Polymorphisms and Risk of Keratoconus

Purpose: Keratoconus (KC) is a genetically heterogeneous corneal dystrophy with unknown etiology that causes loss of visual acuity. Evidence has shown that corneas from patients with KC contain reduced amounts of total collagen proteins, and collagen type IV has been suggested as a candidate gene in KC pathogenesis. This study aimed to evaluate the possible associations between collagen type IV alpha-4 chain (COL4A4) polymorphisms (rs2229813 G/A, M1327V and rs2228555 A/G, V1516V) and susceptibility to KC. Methods: A total of 262 Iranian subjects including 112 patients with KC and 150 healthy individuals as controls were recruited in this case-control study. Diagnosis was based on clinical examination, electronic refractometry, and keratometry. Genotyping for the COL4A4 rs2229813 and rs2228555 variants was executed using allele-specific polymerase chain reaction and Tetra-ARMS polymerase chain reaction, respectively. Results: A significant difference was found between the 2 groups regarding allelic and genotyping distribution of COL4A4 polymorphism at position rs2229813 G>A. The COL4A4 rs2229813 AA and GA+ AA genotypes were risk factors for developing KC (odds ratio [OR] = 2.1, P = 0.036 and OR = 1.7, P = 0.042, for the AA and GA+ AA genotypes, respectively). The COL4A4 rs2229813 A allele was also associated with an increased risk for KC (OR = 1.5, 95% confidence intervals: 1.1-2.2, P = 0.018). However, in our study, we found no association between COL4A4 rs2228555 polymorphism and the risk of KC. Conclusions: We suggest that the COL4A4 rs2229813 AA and GA+ AA genotypes as well as the A allele play roles as risk factors for developing KC in our population.