Ethnic Differences in Cytotoxic T Lymphocyte Associated Antigen 4 Genotype Associations with Systemic Sclerosis

LORI L. HUDSON, RICHARD M. SILVER, and JANARDAN P. PANDEY

ABSTRACT.

Objective. To determine the role of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) genetic polymorphisms in susceptibility to systemic sclerosis (SSc, scleroderma).

Methods. The study population consisted of 293 African American and Caucasian patients with SSc and matched controls. Subjects were genotyped for allelic determinants at 4 polymorphic sites: 3 in the promoter region (positions –318, –1661, –1722) and one in the first exon (position +49) of the CTLA-4 gene, using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Genotype frequencies were compared using Pearson's chi-square or Fisher's exact test.

Results. In African American patients, the frequency of AG heterozygotes at position +49 was significantly higher than in controls (71% vs 36%, p = 0.003; OR = 4.37), while the frequency of AA homozygotes was significantly lower in patients than in controls (29% vs 61%, p = 0.007; OR = 0.26). The distribution of CTLA-4 alleles at other loci did not differ significantly between patients and controls. CTLA-4 genotypes were not associated with SSc in Caucasians. No differences in CTLA-4 genotype distributions were observed between patients with the limited and diffuse forms of the disease.

Conclusion. Our data show that the exon 1 (+49) polymorphism of the CTLA-4 gene is associated with systemic sclerosis in African Americans. (J Rheumatol 2004;31:85-7)

Key Indexing Terms:

SCLERODERMA
T CELL ACTIVATION
AUTOIMMUNITY
SINGLE NUCLEOTIDE POLYMORPHISMS
LINKAGE DISEQUILIBRIUM

---

From the Department of Microbiology and Immunology, and the Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Supported in part by funds from the U.S. Department of Energy cooperative agreement DE-FC02-09CH11109.

L.L. Hudson, BSc, Graduate Student; R.M. Silver, MD, Professor of Medicine; J.P. Pandey, PhD, Professor of Microbiology and Immunology.

Address reprint requests to L.L. Hudson, Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425-2230, USA. E-mail: hudsonll@musc.edu

Submitted January 28, 2003; revision accepted June 9, 2003.

---