Association of FOXE3-p.Ala170Ala and PITX3-p.Ile95Ile polymorphisms with congenital cataract and microphthalmia

Abstract

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.

Deciphering the association of intronic single nucleotide polymorphisms of crystallin gene family with congenital cataract

“…Even if the intronic SNP does not have a functional consequence, it may exist in linkage disequilibrium with other functional SNPs and thereby help recognize the disease loci. Considering the potential association of SNPs with congenital cataract and the dearth of information on genetic association studies using intronic SNPs,[ 38 39 ] the present study was performed to understand the distribution of intronic SNPs rs3788059 ( CRYAA ), rs2070894 ( CRYAB ), rs2071861 ( CRYBA4 ), rs5752083 ( CRYBB2 ), and rs5996863 ( CRYBB2 ) in congenital cataracts and normal healthy controls. Although association studies using these markers have never been reported in congenital cataracts, studies on rs2070894 concerning colorectal and oral cancer[ 40 41 ] and rs2071861 concerning high myopia[ 42 43 ] have been reported.…”