Association between single nucleotide polymorphisms in exon 3 of the alpha-A-crystallin gene and susceptibility to age-related cataract

ABSTRACT

Background

The mutations in the αA-crystallin (CRYAA) gene may contribute to the development of age-related cataract (ARC). In this study, we searched for single nucleotide polymorphisms (SNP) in exons of CRYAA and investigated the associations between the identified SNPs and the subtypes of ARC.

Materials and methods

Peripheral venous blood was collected for the extraction of genomic DNA. Three exons of CRYAA were sequenced to detect SNPs. The frequency distributions of alleles and genotypes were compared between the ARC and control groups.

Results

There were 618 patients with various subtypes of ARC (nuclear cataract [NC], cortical cataract [CC], posterior subcapsular cataract [PSC]). The control group comprised 236 patients. The incidence of early-onset cataract was significantly greater in PSC patients (P = .002 for NC; P = .036 for CC). One SNP was detected in exon 3 of CRYAA (rs76740365 G>A). When the distribution of rs76740365 was compared among the ARC subtypes, only the difference between the PSC group and the control group was statistically significant (allele frequency: P = .000057, OR 2.945; genotype distribution frequency: P = .000458). The heterozygote genotype (GA) carried a significantly greater risk than the homozygous wild-type genotype (GG) by 1.742 times for all types of cataracts and 2.369 times for the PSC subtype.

Conclusions

The SNP rs76740365 G>A in exon 3 of the CRYAA gene is associated with greater susceptibility of ARC, particularly the PSC subtype. Individuals carrying the SNP rs76740365 G>A may be more likely to develop PSC at a younger age than other subtypes.

KEYWORDS:

• Age-related cataract
• CRYAA
• posterior subcapsular cataract
• single nucleotide polymorphism
• exon 3
• missense mutation

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

This work was supported by the Shanghai Science and Technology Commission under Grant 20ZR1410100, the Natural Science Foundation of China under Grant NSFC 81870642, NSFC 81470613, NSFC 81670835, and NSFC 81600719.