Association study of 3 rheumatoid arthritis risk loci in systemic sclerosis in European Caucasian population.

Abstract

INTRODUCTION:

Accumulating evidences show that shared autoimmunity is critical for the pathogenesis of many inflammatory rheumatic conditions. Specific phenotype could arise from specific genes, and/or combination of genetic factors and environment. Systemic sclerosis (SSc) belongs to connective tissue disorders and recent data have highlighted strong associations with some autoimmunity genes shared with other autoimmune diseases.

OBJECTIVES:

To determine whether novel risk loci associated with rheumatoid arthritis (RA) may confer susceptibility to SSc. Single nucleotide polymorphism from CCL21, CD244 and CDK6 were tested for association.

METHODS:

SNPs harbouring association with RA, CCL21-rs2812378, CDK6-rs42041 and CD244-rs6682654 were genotyped in a cohort of 1031 SSc patients and 1014 controls. All individuals were of European Caucasian origin.

RESULTS:

The three polymorphisms were in Hardy-Weinberg equilibrium in the control population and allelic frequencies were similar to those expected in European populations. Allelic and genotypic frequencies for these three polymorphisms were found to be similar in SSc patients and controls. Moreover, sub-phenotype analyses in particular for subgroups having diffuse subcutaneous subtype, specific auto-antibodies or fibrosing alveolitis did not detect any difference between SSc patients and controls.

CONCLUSIONS:

These results obtained through a large cohort of European Caucasian SSc patients do not support the implication of CCL21, CD244 and CDK6 genes in the pathogenesis of SSc although these genes were recently identified as RA susceptibility genes.

• Authors: Baptiste Coustet, Philippe Dieude, Julien Wipft, Jerome Avouac, Eric Hachulla, Elisabeth Diot, Jean-Luc Cracowski, Kiet-Phong Tiev, Jean Sibilia, Luc Mouthon, Camille Frances, Zahir Amoura, Patrick Carpentier, Olivier Meyer, Andre Kahan, Catherine Boileau, Yannick Allanore
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2011 Mar-Apr Vol. 29 Issue 2 Suppl 65 Pg. S6-9 ISSN: 0392-856X [Print] Italy
• PMID: 21586211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• CCL21 protein, human
• CD244 protein, human
• Chemokine CCL21
• Receptors, Immunologic
• Signaling Lymphocytic Activation Molecule Family
• CDK6 protein, human
• Cyclin-Dependent Kinase 6

Topics

• Adult
• Antigens, CD (genetics, immunology)
• Arthritis, Rheumatoid (complications, genetics, immunology)
• Autoimmunity (genetics)
• Chemokine CCL21 (genetics, immunology)
• Cyclin-Dependent Kinase 6 (genetics, immunology)
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, Immunologic (genetics, immunology)
• Scleroderma, Systemic (etiology, genetics, immunology)
• Signaling Lymphocytic Activation Molecule Family
• White People