The role of microvascular endothelial dysfunction and genetics on severity and progression of primary open angle glaucoma in Malays
There is lack of knowledge of clinical presentation and risk factor for primary open angle glaucoma (POAG) in Malays. Identification of the risk factors for severity and progression of POAG in Malays is important to strategies prevention of blindness and effective management. This study was co...
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| Format: | Thesis |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | http://eprints.usm.my/44300/1/Dr.%20Syed%20Mudassar%20Imran%20Bukhari-24%20pages.pdf |
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| Summary: | There is lack of knowledge of clinical presentation and risk factor for primary open
angle glaucoma (POAG) in Malays. Identification of the risk factors for severity and
progression of POAG in Malays is important to strategies prevention of blindness
and effective management. This study was conducted to determine the severity and
progression of POAG in Malay patients and to determine the role of microvascular
endothelial function and genetics in progression and severity of POAG.
A cross-sectional study was conducted involving 215 Malay (114 POAG patients and
101 controls) subjects. Progression was determined based on Humphrey visual field
analysis (HVF) of 114 POAG patients using combination criteria of Advanced
Glaucoma Intervention Study (AGIS) scoring and Hodapp, Parish and Anderson
classification. Severity of POAG was based on modified AGIS scoring of HVF.
Microvascular endothelial function was assessed using Laser Doppler Fluximetry
(LDF) with the process of acetylcholine (ACh) and sodium nitroprusside
iontophoresis. Venesection was also conducted. High purity genomic DNA was
extracted. Microarray Human Omni Express-12 platform was used to identify genetic
markers. rs1392912 and rs1660029 from KALRN gene, and rs1210977of COL9A1
gene were identified as potential markers for progression and microvascularendothelial function. These single nucleotide polymorphisms (SNPs) were then
subjected to DNA sequencing.
After the mean 4.1(3.0) years of follow up, 35 patients showed evidence of visual
field progression. Based on HVF at recruitment, 55 patients were mild, 29 moderate
and 30 severe POAG. There was significant reduction of microvascular endothelial
function in POAG patients compared to control (p<0.001)). ACh and sodium
nitroprusside response was significantly reduced in severe POAG (p<0.001). There
was significant reduction of microvascular endothelial function in patients who
showed visual field progression (p<0.001). The risk of progression is 4.8 folds (95%
CI 1.52, 14.86) in patients with rs1392912GA and 5.8folds (95% CI 1.85, 18.61) in
patients with rs1660029AG. However, there was no association betweenrs1210977
of COL9A1 and microvascular endothelial function of Malay patients with POAG
The progression rate of POAG in Malay patients was 8.5 patients/year.
Microvascular endothelial function play a role in progression and severity of POAG
in Malays. rs1392912GA and rs1660029AG of KALRN gene are potential genetic
markers for progression of glaucoma. Perhaps, improvement in microvascular
endothelial function and early detection of patients with genetic variations of
KALRN gene may retard the progression of POAG in Malays. |
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