Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract

Cui, Xian-Jin; Lv, Feng-Yan; Li, Fenghua; Zeng, Kaiyang

doi:10.1097/md.0000000000007158

Cited by 7 publications

(2 citation statements)

References 18 publications

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“…[ 1 ] Both disorders occur either in isolation or as part of a syndrome and are highly heterogeneous. [ 1 4 ] Several chromosomal, monogenic, and environmental factors have been identified as causes for the occurrence of congenital cataract and microphthalmia. [ 1 5 6 ] Nevertheless, genetic causes have been suggested to play a major role in these conditions.…”

Section: Introductionmentioning

confidence: 99%

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

Vidya¹,

Ganatra

Vasavada

et al. 2018

J Ophthalmic Vis Res

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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.

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Section: Introductionmentioning

confidence: 99%

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

Vidya¹,

Ganatra

Vasavada

et al. 2018

J Ophthalmic Vis Res

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“…[ 20 ] Although the majority of mutations that were identified till date in human congenital cataract is in crystallin genes,[ 17 ] only a few studies have reported the association of intronic SNPs of crystallin genes with congenital cataract. [ 15 21 22 23 ] Furthermore, all these studies have been performed in different ethnic groups and different cohorts of the Indian population. In all these studies, the population from the western region of India was always kept isolated.…”

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confidence: 99%

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

Nair

Sankaranarayanan²,

Vasavada³

2021

Indian Journal of Ophthalmology

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Purpose: Introns play an important role in gene regulation and expression. Single nucleotide polymorphisms (SNPs) in introns have the potential to cause disease and alter the genotype–phenotype association. Hence, this study aimed to decipher the association of SNPs in the introns of the crystallin gene in congenital cataracts. Methods: SNPs in the introns of crystallin gene family – CRYAA (rs3788059), CRYAB (rs2070894), CRYBA4 (rs2071861), and CRYBB2 (rs5752083, rs5996863) – were genotyped in 248 participants consisting of 141 congenital cataracts and 107 healthy controls by allele-specific oligonucleotide polymerase chain reaction method. Around 10% of samples for each SNPs were sequenced to confirm the genotypes. The allele, genotype, and haplotype frequency were evaluated by the SHEsis online tool. Results: Using dominant model, the “A” allele of rs3788059 was found to have an increased risk toward congenital cataract development whereas the “G” allele was found to be protective (AA + AG vs. GG; odds ratio [ OR ] 95% confidence interval [CI] = 3.73 [1.71, 8.15], P = 0.0009). The “A” allele of both rs2070894 (AA + AG vs. GG; OR [95% CI] = 0.49 [0.29, 0.84], P = 0.012) and rs5752083 (AA + AC vs. CC; OR [95% CI] = 0.25 [0.08, 0.76], P = 0.016) were suggested to have a protective role by the dominant model. The A-C-T haplotype (rs2071861, rs5752083, and rs5996863) was found to be a significant risk factor for the development of congenital cataract. Conclusion: Intronic SNPs in crystallin genes may play a role in the predisposition toward congenital cataract. However, the present findings need to be replicated in a large cohort with more number of samples.

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Decreased sialylation elicits complement‐related microglia response and bipolar cell loss in the mouse retina

Cuevas‐Rios,

Assale,

Wissfeld

et al. 2024

Glia

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Sialylation plays an important role in self‐recognition, as well as keeping the complement and innate immune systems in check. It is unclear whether the reduced sialylation seen during aging and in mice heterozygous for the null mutant of UDP‐N‐acetylglucosamine 2‐epimerase/N‐acetylmannosamine kinase (Gne+/−), an essential enzyme for sialic acid biosynthesis, contributes to retinal inflammation and degeneration. We found a reduction of polysialic acid and trisialic acid expression in several retinal layers in Gne+/− mice at 9 months of age compared to Gne+/+ wildtype (WT) mice, which was associated with a higher microglial expression of the lysosomal marker CD68. Furthermore, the total number of rod bipolar cells was reduced in 12 months old Gne+/− mice in comparison to WT mice, demonstrating loss of these retinal interneurons. Transcriptome analysis showed up‐regulation of complement, inflammation, and apoptosis‐related pathways in the retinas of Gne+/− mice. Particularly, increased gene transcript levels of the complement factors C3 and C4 and the pro‐inflammatory cytokine Il‐1β were observed by semi‐quantitative real‐time polymerase chain reaction (sqRT‐PCR) in 9 months old Gne+/− mice compared to WT mice. The increased expression of CD68, loss of rod bipolar cells, and increased gene transcription of complement factor C4, were all prevented after crossing Gne+/− mice with complement factor C3‐deficient animals. In conclusion, our data show that retinal hyposialylation in 9 and 12 months old Gne+/− mice was associated with complement‐related inflammation and lysosomal microglia response, as well as rod bipolar cells loss, which was absent after genetic deletion of complement factor C3.

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Correlations of single nucleotide polymorphisms of CRYAA and CRYAB genes with the risk and clinicopathological features of children suffering from congenital cataract

Cited by 7 publications

References 18 publications

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

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

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

Decreased sialylation elicits complement‐related microglia response and bipolar cell loss in the mouse retina

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