title: Roles of tumor necrosis factor alpha gene polymorphisms, tumor necrosis factor alpha level in aqueous humor, and the risks of open angle glaucoma: a meta-analysis.
abstract: OBJECTIVE
  This meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-α) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-α level in aqueous humor (AH) and the risks of glaucoma.
  
  
  METHODS
  A computerized literature search was performed for the relevant available studies from three databases including PubMed, ISI Web of Science, and Embase. The fixed or random effect model was selected based on the heterogeneity test using the Q test and the I(2) statistic. The associations between TNF-α gene polymorphisms and OAG risks were estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval (CI), while a pooled standardized mean difference with 95% CI was used for the comparison of TNF-α levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test.
  
  
  RESULTS
  A total of 14 (1,182 cases and 3,003 controls), five (808 cases and 1,039 controls), three (645 cases and 666 controls), and three studies (404 cases and 625 controls) were finally included in the analyses for the associations between TNF-α -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-α -308G/A gene polymorphism was significantly associated with risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456; AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms was significantly associated with OAG risks. Furthermore, the pooled results of six studies showed that the TNF-α levels in the AH of patients with OAG was higher than that of the control subjects (standardized mean difference=0.517, 95% CI=0.207-0.826, p=0.001). Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test.
  
  
  CONCLUSIONS
  This meta-analysis suggests that patients with OAG may have higher TNF-α levels compared with the control subjects, and the TNF-α -308G/A polymorphism is significantly associated with the risks of high-tension glaucoma. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.
authors.affiliation: First Center Clinical College, Tianjin Medical University, Tianjin, P R China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xin
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Sun
mesh_terms: D000368:Aged; D001082:Aqueous Humor / Q000378:metabolism*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
references.citation: Ophthalmic Res. 2012;47(1):47-51
references.pmid: 21701244
references.citation: Mol Vis. 2009 Dec 22;15:2861-7
references.pmid: 20029655
references.citation: Br J Ophthalmol. 2006 Mar;90(3):262-7
references.pmid: 16488940
references.citation: Diagn Mol Pathol. 2000 Sep;9(3):158-64
references.pmid: 10976723
references.citation: Eye (Lond). 2003 Jan;17(1):31-4
references.pmid: 12579167
references.citation: Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):241-7
references.pmid: 22159018
references.citation: Prog Brain Res. 2008;173:409-21
references.pmid: 18929124
references.citation: Am Fam Physician. 2003 May 1;67(9):1937-44
references.pmid: 12751655
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: Hum Immunol. 2001 Nov;62(11):1191-9
references.pmid: 11704281
references.citation: Clin Ophthalmol. 2011;5:553-6
references.pmid: 21607023
references.citation: Prog Retin Eye Res. 2003 May;22(3):253-75
references.pmid: 12852486
references.citation: J Sci Food Agric. 2012 Jul;92(9):1892-902
references.pmid: 22234974
references.citation: Eye (Lond). 2006 Sep;20(9):1040-3
references.pmid: 16138112
references.citation: Mol Vis. 2008;14:1815-8
references.pmid: 18852869
references.citation: J Neuroinflammation. 2012 Oct 10;9:235
references.pmid: 23050663
references.citation: Glia. 2000 Oct;32(1):42-50
references.pmid: 10975909
references.citation: Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4359-67
references.pmid: 15557444
references.citation: Indian J Ophthalmol. 2012 Jul;60(4):255-61
references.pmid: 22824592
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):903-6
references.pmid: 19737888
references.citation: Arch Ophthalmol. 2000 May;118(5):666-73
references.pmid: 10815159
references.citation: Clin Exp Ophthalmol. 2012 May-Jun;40(4):e156-62
references.pmid: 21575121
references.citation: Middle East Afr J Ophthalmol. 2011 Jan;18(1):30-6
references.pmid: 21572731
references.citation: J Neurosci. 2006 Dec 6;26(49):12633-41
references.pmid: 17151265
references.citation: Stat Med. 2006 Oct 30;25(20):3443-57
references.pmid: 16345038
references.citation: Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):193-209
references.pmid: 12787559
references.citation: Mol Vis. 2012;18:779-85
references.pmid: 22509108
references.citation: Mol Vis. 2009;15:518-22
references.pmid: 19279689
references.citation: Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4110-6
references.pmid: 20357201
references.citation: Mol Vis. 2012;18:431-8
references.pmid: 22355254
references.citation: Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6441-7
references.pmid: 20592224
references.citation: J Neurosci. 2000 Dec 1;20(23):8693-700
references.pmid: 11102475
references.citation: Ophthalmic Res. 2009;42(3):118-24
references.pmid: 19556827