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

ABSTRACT

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.