Association of tumour necrosis factor-alpha −308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis

Abstract

The objective was to analyze the possible involvement of tumour necrosis factor-alpha (TNF-α) -308 G/A promoter polymorphism in the susceptibility and/or the disease profile of rheumatoid arthritis (RA) in Egyptian patients. TNF-α-308 G/promoter polymorphism detection by amplification refractory mutation system (ARMS) technique was carried out for 122 RA patients and 120 healthy controls. TNF-α-308 G allele/GG homozygous genotype were higher in patients with rheumatoid arthritis than those in control group (P < 0.001, respectively). A statistically significant association was found between the frequency of the A allele and presence of erosion (OR = 3.42, P = 0.015). No associations were found between the distribution of TNF-α-308 G/A alleles/genotypes and age of patients, disease duration, absence of remission, presence of deformity, clinical manifestations of the disease and presence or absence of rheumatoid factor. The positivity of rheumatoid factor was associated with occurrence of erosion (OR = 25.0, P < 0.001). The results of this study demonstrate the association of the TNF-α-308 G allele and GG homozygous genotype with susceptibility to RA and the A allele with the presence of erosion in the Egyptian patients.

Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis

“…In order to be included in this meta-analysis, studies had to 1) include RA patients according to the ACR criteria, and 2) report on disease severity (presence or absence of erosions). Review manager 5 was used to perform a meta-analysis including 11 studies (10 published ones and this study) [1-10]. …”

“…Several genetic variants in the TNFA gene, which codes for TNFα, have been investigated in relation to disease severity, but none of them appears to be highly specific and/or sensitive. The most thoroughly investigated TNFA polymorphism is the -308G > A (rs1800629) located in the promoter of the gene, though studies focusing on this polymorphism have yielded conflicting results, [1-14]. …”

“…Other studies reported a worse radiologic outcome in patients carrying the A allele [1,9,13], or no association between the genetic variant and radiologic progression [2,8-12,14]. Given the contradictory results in these relatively small, individual studies, there is a need for a more comprehensive approach to evaluate the presence or absence of an association between the TNFA -308G > A polymorphism and the severity of RA and radiological joint damage.…”

TNF-α gene polymorphisms and expression

“…For example, susceptibility to RA was associated with the −308A allele in some studies (JimÊnez-Morales et al 2009; Lee et al 2007), with the G allele in others (Mosaad et al 2011), but neither with A allele nor G allele in others (Ates et al 2008; Gambhir et al 2010; Khanna et al 2006; Nemec et al 2008; Rezaieyazdi et al 2007). …”

“…RA severity was associated with the presence of −308A allele (Mosaad et al 2011; Rodríguez-Carreón et al 2005) and with −308G allele (Nemec et al 2008). The −308G allele showed a trend toward worse radiological outcome by 5 years in patients with inflammatory arthritis as indicated by the presence/absence of erosions (Barton et al 2004).…”