First Release: Single-Nucleotide Polymorphisms in CCL2 Gene Are Not Associated with Susceptibility to Systemic Sclerosis

Single-Nucleotide Polymorphisms in CCL2 Gene Are Not Associated with Susceptibility to Systemic Sclerosis

MARIA TERESA CARULLI, PAOLO SPAGNOLO, CARMEN FONSECA, KENNETH I. WELSH, ROLAND M. duBOIS, CAROL M. BLACK, and CHRISTOPHER P. DENTON

ABSTRACT.

Objective. To validate the reported association between CC chemokine ligand 2 (CCL2) -2518 G single nucleotide polymorphism and systemic sclerosis (SSc) in a much larger cohort of patients. We also performed subgroup analysis to test the hypothesis that CCL2 variants predispose to specific disease phenotypes.

Methods. Ninety-four Caucasian patients with SSc and 102 matched controls were genotyped by sequence-specific primers-polymerase chain reaction (SSP-PCR) methodology.

Results. Six biallelic single-nucleotide polymorphisms (SNP) were investigated (3 in the promoter region, 2 in the exon-coding sequence, and 1 in the 3× untranslated region), in addition to the known functional -2518 (A/G) variant. Six major haplotypes were constructed across all 7 SNP positions. No significant differences in genotype, allele, or haplotype frequency were observed between patients and controls or within disease subgroups.

Conclusion. Genetic polymorphisms within CCL2 gene are associated with susceptibility neither to SSc nor to specific disease phenotypes. (J Rheumatol First Release Mar 15 2008)

Key Indexing Terms:

CHEMOKINES
GENETIC POLYMORPHISMS
SYSTEMIC SCLEROSIS
SCLERODERMA
SINGLE-NUCLEOTIDE POLYMORPHISM
CCL2

From the Centre for Rheumatology, Royal Free Hospital and University College Medical School; and the Clinical Genomic Group, National Heart and Lung Institute, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, London, UK.

M.T. Carulli, MD; C. Fonseca, MD, PhD; C.M. Black, MD; C.P. Denton, MD, PhD, Centre for Rheumatology, Royal Free Hospital and University College Medical School; P. Spagnolo, MD, PhD; K.I. Welsh, PhD; R.M. duBois, MD, Clinical Genomic Group, National Heart and Lung Institute, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine.

Address reprint requests to Prof. C.P. Denton, Centre for Rheumatology, Royal Free Hospital and University College Medical School, Rowland Hill Street, Hampstead, London, UK. E-mail: c.denton@medsch.ucl.ac.uk

Accepted for publication December 12, 2007.