Association of interferon-gamma and tumor necrosis factor alpha polymorphisms with susceptibility to vitiligo in Iranian patients

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.

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

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

Al-Harthi

Zouman²,

Arfin³

et al. 2013

“…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.…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

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

Lee

Bae

2015

ABSTRACT. We investigated whether the tumor necrosis factor-a (TNF-α) promoter -238 A/G and -308 A/G polymorphisms are associated with rheumatoid arthritis (RA) and vitiligo susceptibility. MEDLINE and EMBASE databases and a manual search were used to identify articles in which TNF-α polymorphisms were determined in RA or vitiligo patients and controls. Meta-analysis was used to examine the associations between the TNF-α -238 A/G polymorphism and RA and vitiligo using the allelic contrast and dominant models. Fifteen studies (10 RA and 5 vitiligo) involving 3678 cases and 4400 controls were considered. We observed an association between the TNF-α -238 A allele and RA when all subjects were considered [odds ratio (OR) = 0.686, 95% confidence interval (CI) = 0.476-0.968, P = 0.043]. After stratification by ethnicity, we found no association between the TNF-α -238 A allele and RA in European or Asian populations. We observed no association between the TNF-α -308 A allele and vitiligo (OR = 1.787, 95%CI = 0.894-3.573, P = 0.101). However, the adjusted OR by the 5549 TNF-a polymorphisms, and RA, vitiligo ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5548-5559 (2015) trim-and-fill technique was significant (OR = 2.064, 95%CI = 1.138-3.743). After stratification by geographic continent, the TNF-α -308 A allele was significantly associated with vitiligo in Middle Eastern populations (OR = 1.569, 95%CI = 1.224-2.013, P = 3.8 x 10 -5 ). The TNF-α -238 A/G polymorphism was associated with RA susceptibility, and the TNF-a -308 A/G polymorphism may be a significant risk factor for vitiligo in Middle Eastern populations.

“…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.…”

Section: Introductionmentioning

confidence: 98%

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

Nie¹,

Jh²,

Cw³

et al. 2015

ABSTRACT. Several case-control studies have been conducted to investigate the association between the tumor necrosis factor-α (TNF-α)-308G/A polymorphism and vitiligo risk. However, the results of these studies are inconsistent; therefore, we attempted to comprehensively evaluate the association between TNF-α-308G/A polymorphism and vitiligo risk via a meta-analysis. Studies reporting the association between TNF-α-308G/A polymorphism and vitiligo risk were retrieved from PubMed and EmBase databases. Data were extracted from these studies and the pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association. Six case-control studies including 1391 vitiligo cases and 2455 control subjects were included in this meta-analysis. The overall results showed the lack of a significant difference in TNF-α-308G/A genotype distribution between the patients and controls when the G allele and GG, GG + GA, GG, and GG genotypes were compared against the A allele and the GA + AA, AA, AA, and GA genotypes, respectively (ORs = 0.65, 0.53, 0.63, 0.41, 0.55; P = 0.188, 0.121, 0.627, 0.264, 0.135, respectively). This meta-analysis suggests that the TNF-α-308G/A polymorphism may not be associated with vitiligo risk. As few studies are available in this field and current evidence remains limited, these results must be corroborated with well-designed and larger studies in the future.