TNF-α promoter polymorphisms and primary open-angle glaucoma

Abstract

Purpose Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-a (TNF-a) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-a À308G4A and À238G4A gene polymorphisms and the presence of POAG in a Caucasian population. Methods The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-a À308G4A and À238G4A polymorphisms was performed using polymerase chain reaction. Results Allelic frequencies and genotype distributions of both the TNF-a À308G4A and À238G4A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-a À308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-a À238A-allele. Conclusion Our data suggest that none of the investigated TNF-a gene polymorphisms is a major risk factor among Caucasian patients with POAG.

TNF-α -308 A/G and -238 A/G polymorphisms and susceptibility to glaucoma: a meta-analysis

“…Furthermore, the TNF-α -308 A/G and -238 A/G polymorphisms are associated with several autoimmune disorders (Lee et al, 2006a(Lee et al, , 2007(Lee et al, , 2012. However, studies of the associations between these two polymorphisms and glaucoma have reported conflicting results (Lin et al, 2003;Funayama et al, 2004;Tekeli et al, 2008;Khan et al, 2009;Mossböck et al, 2006Mossböck et al, , 2009Razeghinejad et al, 2009;Fan et al, 2010;Bozkurt et al, 2012;Buentello-Volante et al, 2013), which is not altogether surprising. Persistent difficulties regarding robust and replicable results in genetic association studies are almost certainly attributable to small contributions by genetic phenomena.…”

“…First, genetic heterogeneity for glaucoma may exist in different populations. In fact, genetic association studies on glaucoma have demonstrated genetic heterogeneity (Lin et al, 2003;Funayama et al, 2004;Tekeli et al, 2008;Khan et al, 2009;Mossböck et al, 2006Mossböck et al, , 2009Razeghinejad et al, 2009;Fan et al, 2010;Bozkurt et al, 2012;Buentello-Volante et al, 2013). Second, clinical heterogeneities and differences between patient populations may be responsible.…”

“…Seventy studies were identified using electronic and manual searches, and 11 of these were selected for full-text review based on title and abstract details (Lin et al, 2003;Funayama et al, 2004;Tekeli et al, 2008;Khan et al, 2009;Mossböck et al, 2006Mossböck et al, , 2009Razeghinejad et al, 2009;Fan et al, 2010;Bozkurt et al, 2012;Wang et al, 2012;BuentelloVolante et al, 2013). One study was excluded because it contained other polymorphism data (Wang et al, 2012).…”

“…One study was excluded because it contained other polymorphism data (Wang et al, 2012). Thus, a total of ten studies met our inclusion criteria (Lin et al, 2003;Funayama et al, 2004;Tekeli et al, 2008;Khan et al, 2009;Mossböck et al, 2006Mossböck et al, , 2009Razeghinejad et al, 2009;Fan et al, 2010;Bozkurt et al, 2012;Buentello-Volante et al, 2013) (Figure 1). One of the eight eligible studies contained data from three different glaucoma groups, and was therefore treated independently in the meta-analysis of subtypes of glaucoma (Razeghinejad et al, 2009).…”

“…However, published results are inconsistent (Wilson et al, 1997). Several studies have examined the potential contributions made by TNF-α promoter polymorphisms to glaucoma susceptibility (Lin et al, 2003;Funayama et al, 2004;Tekeli et al, 2008;Khan et al, 2009;Mossböck et al, 2006Mossböck et al, , 2009Razeghinejad et al, 2009;Fan et al, 2010;Bozkurt et al, 2012;Buentello-Volante et al, 2013), but the findings of these studies are mixed, probably owing to small sample sizes and low statistical power.…”