A variation in the promoter region of the gene that encodes connective-tissue growth factor (CTGF) appears to confer susceptibility to systemic sclerosis, reported Dr. Carmen Fonseca of Royal Free and University College Medical School, London, and associates.
The researchers genotyped 500 white patients with systemic sclerosis and 500 healthy, white, unrelated control subjects, screening for a specific polymorphism (G-945C) in the region of the CTGF promoter. Significantly more of the patient group (30%) than the control group (19%) carried the polymorphism, they said in the Sept. 20 issue of the New England Journal of Medicine.
There was a strong association between G-allele homozygotes and the presence of specific antibodies—antitopoisomerase 1 and anticentromere—associated with the disease as well as with interstitial lung fibrosis. Positivity for anticentromere antibody previously has been linked to vascular complications such as isolated pulmonary arterial hypertension, which suggests that “a second mechanism involving CTGF overexpression is playing a role” in systemic sclerosis, they said.
“The effects of CTGF on cell proliferation or extracellular matrix production, if induced within certain vessels, could be plausible explanation for this association,” Dr. Fonseca wrote (N. Engl. J. Med. 2207;357:1210–20).
“Our data clearly show an association between the G-945C polymorphism in CTGF and systemic sclerosis, which renders CTGF a susceptibility gene for this complex disease,” they added.
“These data provide new insight into the pathogenesis of systemic sclerosis, including clues to the mechanisms leading to specific disease subtypes. Moreover, they may also be relevant to mechanisms underlying a wide range of other human disorders with a fibrotic component,” Dr. Fonseca and her associates said.