Association between polymorphism of optic disc related genes and susceptibility to primary open angle glaucoma in Inner Mongolia

Objective:To explore the relationship between the polymorphism of optic disc related genes and the susceptibility to primary open angle glaucoma(POAG)in Inner Mongolia.Methods:A retrospective study was adopted to include 108 patients who were diagnosed as POAG in six hospitals in Hohhot and Baotou from January of 2014 to December of 2016(POAG group).At the same time,120 healthy examinees were included in the control group.1-2 ml of whole blood was collected by use of EDTA anticoagulation tubes from each patient in these two groups.It was required to fully mix EDTA with whole blood in order to extract genomic DNA and place it in the-20℃ refrigerator.Mass spectrometry was used to identify the genotype of single nucleotide polymorphism(SNP)of RFTN1(rs690037),ATOH7(rs7916697,rs3858145),CDC7(rs1192415),CDKN2B(rs1063192)and SIX(rs10483727)in 108 POAG patients and 120 normal controls.χ^(2) test and binary logistic regression were used to analyze the relationship between the genetic polymorphism and the occurrence of POAG.Results:The frequency of G allele at CDKN2B(rs1063192)in POAG group was significantly higher than that in the control group(27%vs.17%),and the difference was of statistical significance[odds ratio(OR)=1.824,95%confidence interval(CI):1.163-2.861,p=.008];As to the comparison in the frequency of allele at the other 7 SNPs between the two groups,the differences were statistically significant(all p>.05).Additive and dominant models at rs1063192 indicated that the individuals with G allele were more susceptible to POAG,and the difference was of statistical significance(p<.05),and recessive models showed that the risk in the individuals with A allele was not significantly reduced,and the difference was of no statistical significance(p>.05).There was no statistically significant difference in the distribution of genotypes at other SNPs between POAG group and the control group(p>.05).Conclusions:The genetic polymorphism of CDKN2B(rs1063192)is associated with the susceptibility to POAG,and G allele may increase the risk for POAG.

The Missing Piece in Glaucoma?

Glaucoma is defined as an optic disc neuropathy meaning the nerve fibers are being atrophied similar to the fate occurring in non-glaucomatous optic atrophies. Furthermore, the nerve fibers are always being destroyed randomly in all the non-glaucomatous optic atrophies. In contrast, the nerve fibers in glaucoma are invariably destroyed in an orderly tandem fashion, from peripheral to central, never randomly. Is glaucoma really an optic disc neuropathy in light of orderly destruction of nerve fibers in glaucoma? The current prevailing theories in glaucoma such as posterior bowing of the lamina cribrosa or cupping can’t explain the orderly destruction of nerve fibers occurring in glaucoma. In fact, there is no biological mechanism acting directly on the nerve fibers or their RGCs which could lead to their orderly destruction. Therefore, there should be some mechanical way, which could result in the orderly destruction of nerve fibers even though this mechanical scenario may have resulted from the direct biological effect of raised IOP on some important component of the optic disc. It is proposed that the border tissue of Elschnig (BT) atrophies due to chronic ischemia caused by raised IOP, and as a result, the lamina cribrosa (LC) begins sinking in the scleral canal—a mechanical problem. Due to sinking of the LC, the nerve fibers get stretched and broken starting with the most peripheral nerve fibers being closest to the edge of the scleral opening and ending with the most central nerve fibers in an orderly tandem fashion. Therefore, in view of the orderly destruction of nerve fibers, glaucoma may not be an optic disc neuropathy but an optic disc axotomy.