Association between HSPA5 Promoter Polymorphisms and a Reduced Risk of Normal Tension Glaucoma

Abstract

Introduction: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure (IOP) are likely to play a role in the pathogenesis of optic neuropathy. The potential similarities between Alzheimer's disease (AD) and NTG in cellular apoptosis leading to neurodegeneration have been shown in recent studies. Heat Shock Protein family A member 5 (HSPA5) promoter polymorphisms have been reported to be associated with a risk of AD. The purpose of our study was to investigate the role of HSPA5 promoter polymorphisms in NTG patients.

Methods: A total of 222 patients with NTG, along with 236 normal controls were enrolled in this study. Genomic DNA was amplified through a polymerase chain reaction (PCR) and identified for the polymorphic HSPA5 (-415 and -370) by Xmn1 and BstY1 restriction digestion, respectively. PCR fragments with potential polymorphic HSPA5 (-180) were subjected to sequence-analyses by a Hex-labeled primer. Genotypes for both NTG patients and control groups were compared for statistically significant differences.

Results: Polymorphisms (-415) G/A and (-180) del/G were completely linked in our population. The genotype and allele frequency distribution at the -415 G/A and -180 del/G sites showed a significant difference between the NTG cases and controls. The genotype frequency of HSPA5 (-415) AA/(-180) GG and the allele frequency of HSPA5 (-415) A/(-180) G were significantly lower (p = 0.04 and p = 0.01, respectively) in the NTG patients when compared with those in the control group. There was no significant difference in genotype or allele frequency distribution of the HSPA5 (-370) C/T between the NTG and control groups. There was a reduced risk of NTG associated with the carriers for the HSPA5 (-415) A/(-180) G allele compared with that in the control population (p = 0.01).

Conclusion: HSPA5 (-415) A and (-180) G allele polymorphisms may be protective factors in the development of NTG.

Keywords: Heat shock protein; Normal tension glaucoma; Polymorphism.