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Cinthi Pillai, Waseem A. Aalam, Timothy Sullivan, Jeffrey M. Liebmann, Roshanak Sharafieh, Mansoor Sarfarazi, Robert Ritch; Genetic Screening of LOXL1 Polymorphisms in Exfoliation Syndrome (XFS) Suspects (XFSS). Invest. Ophthalmol. Vis. Sci. 2012;53(14):1536.
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To assess the potential value of LOXL1 screening in patients with no clinically visible exfoliation material in either eye but with other findings suggestive of XFS.
We genotyped 17 XFSS for 3 single nucleotide polymorphisms (SNPs; rs3825942, rs1048661 and rs2165241) by direct DNA sequencing. Patients were then risk stratified based on the genotypic prevalence in our database. Those homozygous for all 3 SNPs had only one possible haplotype resulting in a defined risk. Heterozygous patients had >1 possible haplotype and, thus, a range of risk was estimated. A "G" allele in rs3825942 (G153D) has the strongest association with XFS and, when combined with a "G" in rs1048661 (R141L) and "T" in rs2165241, the risk of XFS increases to 700 times that of the normal population. This was defined as high risk. Other levels of risk were defined as in the table.
There were 9 women and 8 men (mean age: 59.6±9 years). 5 high risk subjects had GG, GG, TT in R153D, R141L and rs2165241 respectively (GGT haplotype). One patient was classified as medium risk with GA, GG, and CT genotypes. 5 low risk patients had GG, GT, CC genotypes respectively. 2 patients defined as very low risk had genotype AA for G153D. The risk of the remaining 4 patients could not be determined due to their heterozygous genotypes for 2 or more SNPs, resulting in a wide range of possible haplotypes.
This is the first time genetic analysis of LOXL1 polymorphisms has been used for risk stratification of XFSS patients. Although patients homozygous for GGT are at significantly increased risk, determining the prognosis of developing XFS is limited by the low specificity of the genetic markers. Further studies of XFS are warranted to identify markers that may improve the diagnostic yield of genetic screening.
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