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Endothelin axis polymorphisms in patients with scleroderma

2006; Wiley; Volume: 54; Issue: 9 Linguagem: Inglês

10.1002/art.22036

1529-0131

Carmen Fonseca, Elisabetta Renzoni, Piersante Sestini, Panagiotis Pantelidis, Anna L. Lagan, Christopher Bunn, Neil McHugh, Ken I. Welsh, R M du Bois, Christopher P. Denton, Carol M. Black, David Abraham,

Eosinophilic Disorders and Syndromes

Abstract Objective To evaluate the distribution of polymorphisms in the endothelin 1 ( EDN1 ), endothelin receptor A ( EDNRA ) and endothelin receptor B ( EDNRB ) genes in systemic sclerosis (SSc; scleroderma) and SSc subsets. Methods Two hundred five patients with SSc and 255 healthy controls were screened for polymorphisms in EDN1 , EDNRA , and EDNRB , using sequence‐specific primer–polymerase chain reaction. The polymorphisms studied were at the following positions: for EDN1 , −1370 (T‐1370G) of the promoter, +138 of exon 1 (+138 A/−), +85 of exon 3 (E106E), and +23 of exon 5 (K198N); for EDNRA , −231 of exon 1 (G‐231A), and +69(H323H) and +105 (E335E) of exon 6; for EDNRB , +2841 of exon 2 (EDNRB‐3), −2547 of exon 3 (EDNRB‐2), and −2446 of exon 3 (EDNRB‐1). Results No significant differences between the SSc group as a whole and control subjects were observed for any of the investigated polymorphisms in EDN1 , EDNRA , and EDNRB . However, compared with patients with limited cutaneous SSc, patients with diffuse skin involvement had an increased frequency of allele carriage of EDNRB‐1A (76.8% versus 54.4%; P = 0.002), EDNRB‐2A (79.7% versus 60.2%; P = 0.006), and EDNRB‐3G (79.7% versus 56.6%; P = 0.001). Significantly increased carriage frequencies for EDNRA alleles H323H/C and E335E/A were observed in SSc patients with anti–RNA polymerase (anti‐RNAP) antibodies, compared with both anti‐RNAP–negative SSc patients ( P < 0.05) and control subjects ( P < 0.005). Conclusion The finding of associations between endothelin receptors A and B and distinct clinical and immunologic SSc subsets supports the role of endothelin and its receptors in the pathogenesis of SSc. However, these findings and their functional significance need to be confirmed and investigated in future studies.