Analysis of the Interleukin-6 (-174) Locus Polymorphism and Serum IL-6 Levels with the Severity of Normal Tension Glaucoma.
OBJECTIVE
In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG.


METHODS
A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression.


RESULTS
The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06).


CONCLUSIONS
The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.
Department of Ophthalmology, Taichung Veterans General Hospital, National Yang-Ming University, Taichung, Taiwan, ROC.
Ching-Yu
CY
Wang
Chiao-Ying
CY
Liang
Shih-Chao
SC
Feng
Keng-Hung
KH
Lin
Hsin-Nung
HN
Lee
Ying-Cheng
YC
Shen
Li-Chen
LC
Wei
Chia-Jen
CJ
Chang
Min-Yen
MY
Hsu
Yi-Yin
YY
Yang
Chun-Hung
CH
Chiu
Chun-Yuan
CY
Wang
D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007429:Intraocular Pressure; D057066:Low Tension Glaucoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D009898:Optic Disk / Q000000981:diagnostic imaging*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D041623:Tomography, Optical Coherence
C508600:IL6 protein, human; D015850:Interleukin-6; D004247:DNA