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C. V. Wolf, N. Weisschuh, B. Wissinger, E. Gramer, B. Mueller-Myhsok; Candidate-Gene Based Association Study of Hereditary Susceptibility Factors in Normal Tension Glaucoma Patients of German Origin. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5608.
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© ARVO (1962-2015); The Authors (2016-present)
Although glaucoma has a strong genetic basis, little is known about hereditary factors of this disease. Apparently only 3-5% of German primary glaucoma patients harbour a causal gene mutation in one of the known three "glaucoma-genes" (MYOC, OPTN, WDR36) and only few familiar cases seem to follow monogenic mendelian inheritance patterns. Therefore a multigenic model of different susceptibility genes contributing to glaucoma development is assumed. The purpose of this study was to evaluate OPA1, SOD2, PARL, MFN1 and MFN2 as susceptibility genes by determining the association of certain haplotypes with normal tension glaucoma regarding age of onset.
A collective of 184 NTG patients between 16-88 years of age (average age 62 years) of German origin traced back for the third generation was included in this study (112 females, 72 males). All of the exonic, intronic and flanking region of the candidate genes was included to calculate LD-Blocks. These blocks where characterized by tagSNPs which were genotyped by TaqMan SNP Genotyping assays. In addition, two intronic SNPs of the OPA1 gene (IVS8 +4 and IVS8 +32) that have been reported previously to be associated with POAG where included in the study. ANOVA for age at onset was performed using a genotypic test. To assess the validity of the p-values, a total of 100,000 permutations were performed for each SNP.
Except for rs6904443 (downstream region of SOD2) none of the SNPs showed a p-value lower than 0.05. The p-value for rs6904443 was 0.0308.
The SOD2 polymorphism rs6904443 is associated with the age of onset of NTG in the German population, whereas we could not find an association of common haplotype variants of OPA1, PARL, MFN1 and MFN2 or OPA1 IVS8 +4 and IVS8 +32. Further studies in other ethnic populations should be performed to elucidate the relationship between the SOD2 gene and NTG.
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