Exploring Functional Candidate Genes for Genetic Association in German Patients With Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Abstract

Purpose: : Pseudoexfoliation (PEX) syndrome is a generalized elastic microfibrillopathy characterized by fibrillar deposits in intra- and extraocular tissues. Genetic and non-genetic factors are known to be involved in its etiopathogenesis. In this study we focus on six functional candidate genes involved in PEX material deposition and analyze their potential association with PEX syndrome and PEX glaucoma (PEXG).

Methods: : 50 single-nucleotide polymorphisms (SNPs) capturing > 95% of overall genetic variance observed in Europeans at loci for FBN1, LTBP2, MFAP2, TGM2, TGF-b1 and CLU were genotyped in 333 unrelated PEX and 342 healthy individuals of German origin and a genetic association study was performed. To replicate our findings, we genotyped two SNPs of the CLU gene in further 328 unrelated German PEX patients as well as in 209 Italian PEX patients and 190 Italian controls.

Results: : Association with PEX was only observed for the SNP rs2279590 in intron 8 of CLU gene coding for clusterin (corrected P=0.0347, OR=1.34) in our first German cohort. Likewise, a frequent haplotype encompassing the associated risk allele showed nominally significant association. None of remaining SNPs nor SNP haplotypes were associated with PEX. The association found was confirmed in a second German cohort (P =0.0244) but not in the Italian cohort (P =0.7173). In addition, the association with CLU SNP rs2279590 was more significant in German patients with PEX syndrome than with PEXG.

Conclusions: : Genetic variants in the gene encoding clusterin may represent a risk factor for PEX in German patients but not in Italian patients. Variants in FBN1, LTBP2, MFAP2, TGF-b1 and TGM2 do not play a major role in the etiology of PEX syndrome, at least in German patients.

Keywords: anterior segment • genetics • gene screening