Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo

Abstract

ABSTRACT. Vitiligo is an acquired depigmentary disorder of the skin, characterized by multiple susceptibility loci and genetic heterogeneity. The etiology of vitiligo is unknown but several hypotheses, including an autoimmune origin, have been proposed. Tumor necrosis factor (TNF)-α, a pleiotropic proinflammatory cytokine, has been shown to play a critical role in several autoimmune diseases including vitiligo. The aim of present study was to determine the association of TNF-α and -β gene polymorphisms with vitiligo in Saudi patients. TNF-α and -β genes were amplified in 123 Saudi patients and 200 matched controls using polymerase chain reaction to search for polymorphisms involved at positions -308, and intron 1 +252. The frequency of the TNF-α (-308) GA genotype was higher and the frequencies of the GG and AA genotypes were significantly lower in vitiligo patients compared to controls. These findings suggested that genotype GA-positive individuals at position -308 of TNF-α are susceptible to vitiligo, whereas the GG and AA genotypes might exert a protective effect. The frequency of allele A (TNF-α 2-allele) was significantly higher and that of allele G (TNF-α 1-allele) was lower in vitiligo patients compared to controls, indicating an association of allele A with susceptibility to TNF-α and -β polymorphisms in vitiligo vitiligo in Saudi patients. The results of our examination of TNF-β (intron 1 +252) polymorphisms showed a significant increase in the frequency of the GG genotype and allele G (TNF-b 1-allele) in vitiligo patients, suggesting a susceptibility of the GG genotype and allele G for vitiligo. By contrast, the high frequency of the GA genotype in controls might indicate a protective effect. The results of the present study strongly support a link between TNF-α (-308) and -β (intron 1 +252) polymorphisms and vitiligo in Saudi patients.

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

“…TNF-α and TNF-β genes were amplified using an amplification refractory mutation system-PCR methodology to detect any polymorphism involved at positions −308 of TNF-α and +252 in intron 1 of TNF-β gene. PCR amplification was carried out using PuReTaq Ready-to-Go PCR Beads (GE Healthcare, Buckinghamshire, UK) as described elsewhere 32. The molecular analysis of the samples was performed in the same laboratory and at the same time.…”

Associations between TNF-α polymorphisms and susceptibility to rheumatoid arthritis and vitiligo: a meta-analysis

“…Three were excluded because no extractable genotype data or family data were included. Thus, 15 studies met our inclusion criteria (Brinkman et al, 1997;Vinasco et al, 1997;van Krugten et al, 1999;Yen et al, 2001;Fabris et al, 2002;Zwiers et al, 2004;Correa et al, 2005;Rodríguez-Carreón et al, 2005;Yazici et al, 2006;Namian et al, 2009;Emonts et al, 2011;Laddha et al, 2012;Salinas-Santander et al, 2012;Al-Harthi et al, 2013;You et al, 2013). Ten studies examined RA and 5 examined vitiligo.…”

“…The TNF-a -238 A/G and -308 A/G polymorphisms have been reported to be associated with several autoimmune disorders (Lee et al, 2006). However, studies examining the associations between these polymorphisms and RA or vitiligo have shown conflicting results (Brinkman et al, 1997;Vinasco et al, 1997;van Krugten et al, 1999;Yen et al, 2001;Fabris et al, 2002;Zwiers et al, 2004;Correa et al, 2005;Rodríguez-Carreón et al, 2005;Yazici et al, 2006;Namian et al, 2009;Emonts et al, 2011;Laddha et al, 2012;Salinas-Santander et al, 2012;Al-Harthi et al, 2013;You et al, 2013). Persistent difficulties regarding robust and replicable results in genetic association studies are almost certainly attributable to the small size of the effects of genetic variants, and therefore, a large number of study subjects is required to ensure adequate statistical power, such as a meta-analysis.…”

Meta-analysis of the TNF-α-308G/A polymorphism and vitiligo risk

“…The most common polymorphism occurs at position -308 (TNF-α-308G/A), which may affect the cytokine production (Wilson et al, 1997;Louis et al, 1998;Abraham and Kroeger, 1999). A number of case-control studies have been conducted to investigate the association between the TNF-α-308G/A polymorphism and vitiligo risk (Yazici et al, 2006;Namian et al, 2009;Laddha et al, 2012;Salinas-Santander et al, 2012;Al-Harthi et al, 2013;Aydingoz et al, 2015). However, the results of these studies have been inconsistent, which may be attributed to small sample sizes and the differences in ethnic populations.…”