Associations of polymorphisms in LOXL1 and copper chaperone genes with pseudoexfoliation-syndrome-related cataract in a Chinese Uygur population

Purpose To investigate the associations between single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene and copper chaperone genes and pseudoexfoliation-syndrome-related cataract (PEXC) in a Chinese Uygur population. Methods A case-control study was performed at the Second People's Hospital of Kashgar. Venous blood DNA was obtained from 70 patients with PEXC and 70 patients with age-related cataract (ARC). The exonic sequences of the LOXL1, antioxidant 1 copper chaperone (ATOX1), cytochrome C oxidase 17 copper chaperone (COX17), and copper chaperone for superoxide dismutase (CCS) genes were determined by Sanger sequencing, followed by a genetic association study. SIFT and PolyPhen-2 were used to predict the functional effects of the SNPs detected. The protein levels of CCS in lens-capsule specimens were measured by Western blotting. The plasma level of the CCS protein was measured using an enzyme-linked immunosorbent assay. Results Two coding SNPs (rs1048661 and rs3825942) in LOXL1 gene and a non-synonymous risk variant in CCS gene: CCS (c.717C>G, p.Asn239Lys) were significantly associated with PEXC. The TT genotype of rs1048661 was protective against PEXC in this Uygur population. The GG genotype of rs3825942 and its G allele were associated with an increased risk of PEXC. The CC genotype of c.717C>G and its C allele were protective against PEXC. The plasma level of CCS was significantly lower in patients with PEXC compared with those with ARC. Conclusions The rs3825942 SNP of LOXL1 was strongly associated with PEXC in this Uygur population in China. CCS variants may represent a risk factor for PEXC. Our findings expand the understanding of the genetic base of PEXC.