Endothelin axis polymorphisms in patients with scleroderma

Carmen Fonseca, Elizabeth Renzoni, Piersante Sestini, Panagiotis Pantelidis, Anna Lagan, Christopher Bunn, Neil McHugh, Ken I Welsh, Ron M Du Bois, Christopher P Denton, Carol Black, D Abraham

Research output: Contribution to journalArticlepeer-review

48 Citations (SciVal)


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.

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).

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).

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.
Original languageEnglish
Pages (from-to)3034-3042
Number of pages9
JournalArthritis & Rheumatism
Issue number9
Early online date30 Aug 2006
Publication statusPublished - Sept 2006


Dive into the research topics of 'Endothelin axis polymorphisms in patients with scleroderma'. Together they form a unique fingerprint.

Cite this