Purpose We performed a case‐control study to search for genetic interactions and for differences in dry and wet age‐related macular degeneration (AMD) pathogenesis.
Methods We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested.
Results No association was found between either the exudative or the dry form and the genetic backround in the case of Apolipoprotein E, complement factor I, FXIII and MerTK polymorphisms. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR=0.50, 95%CI: 0.26‐0.97, p=0.04). Multiple regression models revealed a genetic interaction in the dry AMD subgroup. In the absence of a C3 risk allele, mutated alleles of both CFH and HTRA1 behaved as strongly significant risk factors (OR=7.96, 95%CI: 2.39=26.50, p=0.0007, and OR=36.02, 95%CI: 3.30‐393.02, p=0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near‐five‐fold relative increase in the odds of dry type AMD(OR=4.93, 95%CI: 1.98‐12.25, p=0.0006)
Conclusion Our results shed light on the protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed in dry AMD pathogenesis.