Full Text: Association of Polymorphisms in the IL1B and IL2 Genes with Susceptibility and Severity of Systemic Sclerosis

Association of Polymorphisms in the IL1B and IL2 Genes with Susceptibility and Severity of Systemic Sclerosis

SILVIA MATTUZZI, STEFANO BARBI, ANTONIO CARLETTO, VIVIANA RAVAGNANI, PATRICK S. MOORE, LISA MARIA BAMBARA, and ALDO SCARPA

ABSTRACT.

Objective. To investigate possible associations of 9 single-nucleotide polymorphisms in the IL10, IL1B, IL1A, IL1RN, IL2, LTA, and IL6 genes with susceptibility to systemic sclerosis (SSc), and with clinical subtype of SSc patients.

Methods. A total of 78 patients with SSc [diffuse SSc (dcSSc), n = 31; limited SSc, (lcSSc), n = 47] and 692 healthy blood donors were genotyped for the following polymorphisms: IL10 T-3575A, IL10 A-1082G, IL1B C-31T, IL1B C-511T, IL1A C-889T, IL1RN A9589T, IL2 T-384G, LTA T-91G, and IL6 G-174C.

Results. Alleles in IL1B-31 and IL1B-511 showed a significantly different distribution between cases and controls. Carriers of at least one copy of the IL1B-31-C allele had an increased risk of SSc [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-5.2, p < 0.001], while a similar strong association was also evident for IL1B-511-T carriers (OR 3.1, 95% CI 1.7-5.7, p < 0.001). Interestingly, carriers of the IL2-384-G allele were significantly more frequent among patients with lcSSc (80.8%), compared to patients with the diffuse subtype (45.1%) (OR 5.1, 95% CI 1.8-14.3, p = 0.001) and in subjects positive to anticentromere antibodies (OR 4.2, 95% CI 1.5-11.9, p = 0.007). Lastly, the distribution of the IL2-384 genotype showed statistically significant differences between controls and patients with lcSSc (OR 3.5, 95% CI 1.7–7.4, p < 0.001). There were no differences between patients with dcSSc and controls.

Conclusion. IL1B and IL2 gene polymorphisms may be involved in susceptibility to SSc. Moreover, the IL2-384-G allele may be a marker for the limited phenotype of SSc. (First Release April 15 2007; J Rheumatol 2007;34:997–1004)

Key Indexing Terms:

SYSTEMIC SCLEROSIS
SINGLE-NUCLEOTIDE POLYMORPHISM
INTERLEUKINS
GENETIC SUSCEPTIBILITY

From the Dipartimento di Patologia and the Dipartimento di Medicina Clinica e Sperimentale, Università di Verona, Verona, Italy.

Supported by Fondazione Cariverona (2004), Verona Italy to Aldo Scarpa. Stefano Barbi is supported by a grant from Fondazione Giorgio Zanotto-Banco Popolare di Verona, Verona, Italy.

S. Mattuzzi, MS, PhD candidate; S. Barbi, PhD, Research Fellow, Dipartimento di Patologia; A. Carletto, MD, Physician; V. Ravagnani, MD, Physician, Dipartimento di Medicina Clinica e Sperimentale; P.S. Moore, PhD, Senior Scientist, Dipartimento di Patologia; L.M. Bambara, MD, Professor, Dipartimento di Medicina Clinica e Sperimentale; A. Scarpa, MD, PhD, Professor, Dipartimento di Patologia, Università di Verona.

Address reprint requests to Dr. A. Scarpa, Dipartimento di Patologia, Università di Verona, Strada Le Grazie 8, 37134 Verona, Italy. E-mail: aldo.scarpa@univr.it

Accepted for publication December 24, 2006.