Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma

• Published in: Rheumatology (Oxford, England) England), 2005-02, Vol.44 (2), p.197-201
• Main Authors: Lagan, A. L., Pantelidis, P., Renzoni, E. A., Fonseca, C., Beirne, P., Taegtmeyer, A. B., Denton, C. P., Black, C. M., Wells, A. U., du Bois, R. M., Welsh, K. I.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Female; Fibrosis; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genotype; Haplotype; Haplotypes - genetics; Humans; Male; Medical sciences; Osteonectin - genetics; Polymorphism, Single Nucleotide - genetics; Pulmonary Fibrosis - complications; Pulmonary Fibrosis - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma; Scleroderma, Diffuse - genetics; Scleroderma, Limited - genetics; Scleroderma, Systemic - complications; Scleroderma, Systemic - genetics; SNP; SPARC
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keh460

Objective. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that modulates cell–cell and cell–extracellular matrix interactions. SPARC expression is restricted mainly to sites of tissue remodelling and wound repair, and is prominent in fibrotic disorders. Single-nucleotide polymorphisms (SNPs) in the SPARC gene are reportedly linked to scleroderma in four ethnic groups: Choctaw Indians, Caucasians, African Americans and Mexican Americans. We set out to reproduce and to positionally clone these disease associations in a set of UK Caucasian scleroderma patients and ethnically matched controls. Methods. One hundred and twenty-one scleroderma subjects and 200 controls were genotyped by polymerase chain reaction with sequence-specific primers differing only in the 3′ nucleotide corresponding to each allele of the biallelic SNPs. Scleroderma patients were analysed against controls and on the basis of their fibrosing alveolitis status as judged by high-resolution computed tomography evaluation and the extent of cutaneous involvement. Results. Eight biallelic SNPs were genotyped: three from the last untranslated exon, which had been described previously, and an additional five novel SNPs: two in the promoter region, one in exon three and two in the 3′ untranslated region. Six major haplotypes were constructed across all eight SNP positions. No significant differences in genotype, allele or haplotype frequency were observed between scleroderma and controls or within scleroderma subgroups. Conclusions. SNPs in the SPARC gene are not associated with susceptibility to scleroderma. This research adds to the genetic knowledge of the SPARC gene by identifying five novel SNPs spanning the whole gene and inserting these within the context of clearly defined haplotypes.