association of foxe3‑p.ala170ala and pitx3‑p.ile95ile polymorphisms with congenital cataract and microphthalmia

Purpose: to investigate the association of foxe3‑p.ala170ala (rs34082359) and pitx3‑p.ile95ile (rs2281983) polymorphisms with congenital cataract and microphthalmia in a western indian population. methods: foxe3‑p.ala170ala (c.510c>t) and pitx3‑p.ile95ile (c.285c>t) polymorphisms were genotyped in 561 subjects consisting of 242 cases with congenital cataract, 52 with microphthalmia, and 267 controls using polymerase chain reaction‑restriction fragment length polymorphism. approximately 10% of samples were randomly sequenced for each single nucleotide polymorphism to confirm the genotypes. the prediction of mrna secondary structure for polymorphism foxe3‑p.ala170ala and pitx3‑p.ile95ile was performed. results: a significantly high frequency of t allele and a borderline significance in the frequency of tt genotype of foxe3‑p.ala170ala was observed in microphthalmia cases, as compared to controls [t allele: or: [ci] = 1.8 [1.15‑2.72], p = 0.0115; tt: or [ci] = 2.9 [1.14‑7.16], p = 0.0291). the frequency of cc genotype was significantly low in microphthalmia cases when compared to controls (cc: or [ci] = 0.5 [0.24‑0.86, p = 0.0150). there was no significant difference in the allele and genotype frequencies of pitx3‑p.ile95ile between cases and controls. a slight free energy change was observed in the secondary structure of mrna between the foxe3‑p.ala170ala c‑allele (‑917.60 kcal/mol) and t‑allele (‑916.80 kcal/mol) and between pitx3‑p.ile95ile c‑allele (‑659.80 kcal/mol) and t‑allele (‑658.40 kcal/mol). conclusion: the present findings indicate that foxe3‑p.ala170ala ‘t’ allele and ‘tt’ genotype could be predisposing factors for microphthalmia while ‘cc’ genotype might play a protective role against it. a reduction in the free energy change associated with foxe3‑p.ala170ala ‘t’ allele could further contribute towards disease risk.