Risk of open angle glaucoma due to tumor necrosis factor alpha gene polymorphisms

Authors

  • Leqaa Moemen Medical Biochemistry Unit, Research Institute of Ophthalmology, Giza, Egypt

Keywords:

open angle glaucoma, TNFα 308G/A polymorphism

Abstract

Introduction: Axonal degeneration and retinal ganglion cell apoptosis in glaucoma is associated with tumor necrosis factor alpha (TNF-α), which is an important pro-inflammatory cytokine. The aim of this study was to determine the association between the risk of open angle glaucoma (OAG) in the Egyptian population and tumor necrosis factor alpha (TNF-α) gene polymorphisms.

Methods: Sixty OAG patients and 26 healthy unrelated controls were used to analyze TNF-α polymorphism G-308A using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results: the GG genotype was found at a higher frequency in the controls than in the patients, and the AA and GA genotypes were associated strongly with OAG. 

Conclusion: In this study, we found that the TNF-α polymorphism G-308A was associated significantly with OAG in the Egyptian population. However, there is a need for population-based studies with large numbers of subjects. Also, long-term follow up is required to verify the association between TNF-α polymorphism G-308A and glaucoma susceptibility.

References

Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J

Ophthalmol. 2006; 90: 262-7. doi: 10.1136/bjo.2005.081224, PMID: 16488940, PMCID: PMC1856963.

Distelhorst JS, Hughes GM. Open-angle glaucoma. Am Fam Physician. 2003; 67: 1937-44. PMID:

Agarwal R, Agarwal P. Glaucomatous neurodegeneration: An eye on tumor necrosis factor-alpha. Indian J

Ophthalmol. 2012; 60: 255. doi: 10.4103/0301-4738.98700, PMID: 22824592, PMCID: PMC3442458.

Dempsey PW, Doyle SE, He JQ, Cheng G. The signaling adaptors and pathways activated by TNF

superfamily. Cytokine Growth Factor Rev. 2003; 14: 193-209. doi: 10.1016/S1359-6101(03)00021-2.

Tezel G. TNF-alpha signaling in glaucomatous neurodegeneration. Prog Brain Res. 2008; 173: 409-21. doi:

1016/S0079-6123(08)01128-X.

Tezel G, Wax MB. Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated

ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells. J Neurosci.

; 20: 8693-700. PMID: 11102475.

Yuan L, Neufeld AH. Tumor necrosis factor-alpha: a potentially neurodestructive cytokine produced by

glia in the human glaucomatous optic nerve head. Glia. 2000; 32: 42-50. doi: 10.1002/1098- 1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3.

Yan X, Tezel G, Wax MB, Edward DP. Matrix metalloproteinases and tumor necrosis factor alpha in

glaucomatous optic nerve head. Arch Ophthalmol. 2000; 118: 666-73. doi: 10.1001/archopht.118.5.666,

PMID: 10815159.

Nakazawa T, Nakazawa C, Matsubara A, Noda K, Hisatomi T, She H, et al. Tumor necrosis factor-alpha

mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J

Neurosci. 2006; 26: 12633-41. doi: 10.1523/JNEUROSCI.2801-06.2006, PMID: 17151265.

Hajeer AH, Hutchinson IV. Influence of TNFalpha gene polymorphisms on TNFalpha production and

disease. Hum Immunol. 2001; 62: 1191-9. doi: 10.1016/S0198-8859(01)00322-6.

Agarwal P, Oldenburg MC, Czarneski JE, Morse RM, Hameed MR, Cohen S, et al. Comparison study for

identifying promoter allelic polymorphism in interleukin 10 and tumor necrosis factor alpha genes.

DiagnMolPathol. 2000; 9: 158-64. doi: 10.1097/00019606-200009000-00006, PMID: 10976723.

Al-Dabbagh NM, Al-Dohayan N, Al-Asmari A, Arfin M, Tariq M. Association of TNF-α and TNF-β Gene

Polymorphisms with Primary Open Angle and Primary Angle Closure Glaucoma. In: Tomas Kubena,

editor. The Mystery of Glaucoma. InTech; 2011; 229-56. doi: 10.5772/19057.

Razeghinejad MR, Rahat F, Kamali-Sarvestani E. Association of TNFA −308 G/A and TNFRI +36 A/G

gene polymorphisms with glaucoma. Ophthalmic Res. 2009; 42: 118-24. doi: 10.1159/000226108, PMID:

Khan MI, Micheal S, Rana N, Akhtar F, den Hollander AI, Ahmed A, et al. Association of tumor necrosis

factor alpha gene polymorphism G-308A with pseudoexfoliative glaucoma in the Pakistani population. Mol

Vis. 2009; 15: 2861-7. PMID: 20029655, PMCID: PMC2796874.

Lin HJ, Tsai FJ, Chen WC, Shi YR, Hsu Y, Tsai SW. Association of tumour necrosis factor alpha −308

gene polymorphism with primary open-angle glaucoma in Chinese. Eye (Lond). 2003; 17: 31-4. doi:

1038/sj.eye.6700227, PMID: 12579167.

Mossböck G, Renner W, El-Shabrawi Y, Faschinger C, Schmut O, Wedrich A, et al. TNF-alpha −308 G>A

and −238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.

Mol Vis. 2009; 15: 518-22. PMID: 19279689, PMCID: PMC2654045.

Mossböck G, Weger M, Moray M, Renner W, Haller-Schober EM, Mattes D, et al. TNF-alpha promoter

polymorphisms and primary open-angle glaucoma. Eye (Lond). 2006; 20: 1040-3. doi:

1038/sj.eye.6702078, PMID: 16138112.

Funayama T, Ishikawa K, Ohtake Y, Tanino T, Kurosaka D, Kimura I, et al. Variants in optineurin gene

and their association with tumor necrosis factor-alpha polymorphisms in Japanese patients with glaucoma.

Invest Ophthalmol Vis Sci. 2004; 45: 4359-67. doi: 10.1167/iovs.03-1403, PMID: 15557444.

Fan BJ, Liu K, Wang DY, Tham CC, Tam PO, Lam DS, et al. Association of polymorphisms of tumor

necrosis factor and tumor protein p53 with primary open-angle glaucoma. Invest Ophthalmol Vis Sci.

; 51: 4110-6. doi: 10.1167/iovs.09-4974, PMID: 20357201.

Tekeli O, Turacli ME, Egin Y, Akar N, Elhan AH. Tumor necrosis factor alpha-308 gene polymorphism

and pseudoexfoliation glaucoma. Mol Vis. 2008; 14: 1815-8. PMID: 18852869, PMCID: PMC2565691.

Chua J, Vania M, Cheung CM, Ang M, Chee SP, Yang H, et al. Expression profile of inflammatory

cytokines in aqueous from glaucomatous eyes. Mol Vis. 2012; 18: 431-8. PMID: 22355254, PMCID:

PMC3283212.

Balaiya S, Edwards J, Tillis T, Khetpal V, Chalam KV. Tumor necrosis factor-alpha (TNF-alpha) levels in

aqueous humor of primary open angle glaucoma. ClinOphthalmol. 2011; 5: 553-6. doi:

2147/opth.s19453.

Takai Y, Tanito M, Ohira A. Multiplex cytokine analysis of aqueous humor in eyes with primary open- angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci. 2012; 53: 241-7. doi:

1167/iovs.11-8434, PMID: 22159018.

Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21: 1539-58.

doi: 10.1002/sim.1186, PMID: 12111919.

Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull. 1999;

: 15-7.

Harbord RM, Egger M, Sterne JA. A modified test for small-study effects in meta-analyses of controlled

trials with binary endpoints. Stat Med. 2006; 25: 3443-57. doi: 10.1002/sim.2380, PMID: 16345038

Zeng T, Guo FF, Zhang CL, Song FY, Zhao XL, Xie KQ. A meta-analysis of randomized, double-blind,

placebo-controlled trials for the effects of garlic on serum lipid profiles. J Sci Food Agric. 2012; 92: 1892- 902. doi: 10.1002/jsfa.5557, PMID: 22234974.

Cui G, Wang H, Li R, Zhang L, Li Z, Wang Y, et al. Polymorphism of tumor necrosis factor alpha (TNF- alpha) gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke. J

Neuroinflammation. 2012; 9: 235. doi: 10.1186/1742-2094-9-235, PMID: 23050663, PMCID:

PMC3521196.

Bozkurt B, Mesci L, Irkec M, Ozdag BB, Sanal O, Arslan U, et al. Association of tumour necrosis factor- alpha −308 G/A polymorphism with primary open-angle glaucoma. Clin Experiment Ophthalmol. 2012;

: e156-62. doi: 10.1111/j.1442-9071.2011.02595.x, PMID: 21575121.

Wang CY, Shen YC, Wei LC, Lin KH, Feng SC, Yang YY,. Polymorphism in the TNF-alpha(−863) locus

associated with reduced risk of primary open angle glaucoma. Mol Vis. 2012; 18: 779-85. PMID:

, PMCID: PMC3324355.

Kuchtey J, Rezaei KA, Jaru-Ampornpan P, Sternberg P, JrKuchtey RW. Multiplex cytokine analysis

reveals elevated concentration of interleukin-8 in glaucomatous aqueous humor. Invest Ophthalmol Vis

Sci. 2010; 51: 6441-7. doi: 10.1167/iovs.10-5216, PMID: 20592224, PMCID: PMC3055764.

Sawada H, Fukuchi T, Tanaka T, Abe H. Tumor necrosis factor-alpha concentrations in the aqueous humor

of patients with glaucoma. Invest Ophthalmol Vis Sci. 2010; 51: 903-6. doi: 10.1167/iovs.09-4247, PMID:

Yu QQ, Yao Y. A detailed meta-analysis shows no association between TNF-alpha −308G/A

polymorphism and different forms of glaucoma. Ophthalmic Res. 2012; 47: 47-51. doi:

1159/000328631, PMID: 21701244.

Published

2022-02-21