Multiple Gene Polymorphisms Associated with Exfoliation Syndrome in the Uygur Population

Abstract

Background. Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods. A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results. The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P<0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P<0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P=0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P<0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P<0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P=0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions. With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations

“…Interestingly, though, Uygur populations in China have higher rates of XFS/XFG—with rates as ranging between 2.2% to 9.5% depending on age [ 214 ]. In these populations, LOXL1 SNPs have similarly been identified as risk alleles for XFS/XFG [ 180 , 215 ]. Uygur populations have also shown association with SNPs of TBC1D21 and ATXN2 [ 216 ].…”

“…In these populations, LOXL1 SNPs have similarly been identified as risk alleles for XFS/XFG [ 180 , 215 ]. Uygur populations have also shown association with SNPs of TBC1D21 and ATXN2 [ 216 ]. Meanwhile, in North Indian populations, rs3925942 has shown a significant association with XFS/XFG [ 217 ], but other SNPs of LOXL1 have shown no association [ 182 ].…”

Recent advances in risk factors associated with ocular exfoliation syndrome

“…; Ma et al. ). Genome‐wide association study (GWASs) and next‐generation sequencing technologies have been used to elucidate potential genetic causal variants underlying XFS, which could help better understanding the disease mechanism and provide specific treatment approaches (Schlötzer‐Schrehardt ).…”

“…Research on the genetic risk factors for XFS is an area of intense research, and other susceptibility loci and SNPs have been identified in association with this syndrome in certain populations (Krumbiegel et al 2011;Wiggs et al 2012;Nakano et al 2014;Zagajewska et al 2018;Ma et al 2019). Genomewide association study (GWASs) and next-generation sequencing technologies have been used to elucidate potential genetic causal variants underlying XFS, which could help better understanding the disease mechanism and provide specific treatment approaches (Schl€ otzer-Schrehardt 2018).…”

The RNA‐binding protein and stress granule component ATAXIN‐2 is expressed in mouse and human tissues associated with glaucoma pathogenesis

“…SCA2 patients may present with visual phenotypes such as retinal nerve fiber layer thinning, night blindness, ophthalmoparesis, ERG abnormalities, retinal dystrophy, and retinitis pigmentosa (Kurashige et al, 2020;Paciorkowski et al, 2011;Pula et al, 2011;Rufa et al, 2002;Volpe et al, 2015), whereas a recent GWAS study associated ATXN2 SNPs with primary open angle glaucoma (POAG), a leading worldwide cause of irreversible blindness (Bailey et al, 2016;Jonas et al, 2017). Additional ATXN2 polymorphisms have been linked to exfoliation glaucoma (Ma et al, 2019). Taking into account ocular phenotypes and pro-apoptotic impairment of autophagosome formation and stress granule clearance in glaucoma and ALS (Becker et al, 2017;Deluca et al, 2017;de Majo et al, 2018;Fingert et al, 2017;Hirt & Liton, 2017;Kurashige et al, 2020;Paciorkowski et al, 2011;Paul et al, 2018;Porter et al, 2013;Pula et al, 2011;Rufa et al, 2002;Scoles et al, 2017;Volpe et al, 2015), it is conceivable that abnormal intracellular transport, translation, stability, and distribution of mRNAs in chronic ocular neuropathologies might involve ATXN2; yet, there is virtually no information about its ocular localization and expression.…”