Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis

Abstract

Many studies have previously confirmed high TNFalpha (tumor necrosis factor-alpha) production in sarcoidosis, and have shown that TNFalpha plays an important role in granuloma formation. We investigated TNFA and TNFB (lymphotoxin-alpha) gene polymorphisms in 26 cardiac sarcoidosis patients of Japanese origin. These studies revealed a significant increase in the more uncommon TNFA2 allele in the patient group, suggesting that the TNFA gene controls the genetic susceptibility to cardiac sarcoidosis.

Role of genetic polymorphisms in ACE and TNF-α gene in sarcoidosis: a meta-analysis

“…However, it has been suggested that the polymorphism could be involved in clinical presentation of sarcoidosis, but these suggestions are contradictory: two studies suggested the allele 2 being associated with erythema nodosum (Löfgren syndrome), whereas one study suggested that the same allele should be associated with cardiac sarcoidosis (Seitzer et al 1997;Takashige et al 1999;Labunski et al 2001). It has to be stressed that two individual reports of the -308/TNF-a polymorphism involvement in sarcoidosis have been performed on specific clinical presentation of sarcoidosis and on a remarkably small number of patients (Takashige et al 1999;Labunski et al 2001). The summary OR performed if excluding these two studies is 1.24 (95% CI 1.02-1.52).…”

“…The characteristics of seven analyses (Seitzer et al 1997;Takashige et al 1999;Somskövi et al 1999;Yamaguchi et al 2001;Labunski et al 2001;Pandey et al 2002;Mrazek et al 2005) on the risk of sarcoidosis in subjects with the -308 polymorphism in the TNF-a gene are summarized in Table 3. These studies involved 901 patients and 1,459 controls.…”

“…(Arbustini et al 1996;Furuya et al 1996;Sharma et al 1997;Tomita et al 1997;Takemoto et al1998;Garrib et al 1998;Maliarik et al 1998;Pietinalho et al 1999;Papadopoulos et al 2000;Planck et al 2002;Alia et al 2005;Csaszar et al1997;Niimi et al1998;Kawakami et al1998;Schurmann et al2001;Rybicki et al2004) 12 (Arbustini et al 1996;Furuya et al 1996;Sharma et al1997;Tomita et al 1997;Takemoto et al 1998;Garrib et al 1998;Maliarik et al 1998;Pietinalho et al 1999;Papadopoulos et al 2000;Planck et al 2002;Alia et al 2005) A-5466C (Rybicki et al2004;Seitzer et al1997;Takashige et al1999;Somskövi et al1999;Yamaguchi et al2001;Labunski et al2001;Grutters et al2002;Pandey et al2002;Mrazek et al2005) 7 (Seitzer et al 1997;Takashige et al 1999;Somskövi et al 1999;Yamaguchi et al 2001;Labunski et al 2001;Pandey et al2002;Mrazek et al2005) -238 3 …”

“…Additionally, there were five case-control studies identified that reported an association of intron 1/tumor necrosis factor-b (TNF-b) polymorphism and sarcoidosis (Seitzer et al 1997;Takashige et al 1999;Yamaguchi et al 2001;Mrazek et al 2005;Ishihara et al 1995), but only three included the data on genotype frequencies. (Arbustini et al 1996;Furuya et al 1996;Sharma et al 1997;Tomita et al 1997;Takemoto et al1998;Garrib et al 1998;Maliarik et al 1998;Pietinalho et al 1999;Papadopoulos et al 2000;Planck et al 2002;Alia et al 2005;Csaszar et al1997;Niimi et al1998;Kawakami et al1998;Schurmann et al2001;Rybicki et al2004) 12 (Arbustini et al 1996;Furuya et al 1996;Sharma et al1997;Tomita et al 1997;Takemoto et al 1998;Garrib et al 1998;Maliarik et al 1998;Pietinalho et al 1999;Papadopoulos et al 2000;Planck et al 2002;Alia et al 2005) A-5466C (Rybicki et al2004;Seitzer et al1997;Takashige et al1999;Somskövi et al1999;Yamaguchi et al2001;Labunski et al2001;Grutters et al2002;Pandey et al2002;…”

“…Of nine studies on TNF-a polymorphisms in sarcoidosis, seven case-control studies on -308 polymorphism were included in the meta-analysis (Seitzer et al 1997;Takashige et al 1999;Somskövi et al 1999;Yamaguchi et al 2001;Labunski et al 2001;Pandey et al 2002;Mrazek et al 2005). One excluded study reported allelic frequencies; the other was family-based study (Rybicki et al 2004;Grutters et al 2002).…”