Ethnic differences in cytotoxic T lymphocyte associated antigen 4 genotype associations with systemic sclerosis.
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.


CONCLUSIONS
Our data show that the exon 1 (+49) polymorphism of the CTLA-4 gene is associated with systemic sclerosis in African Americans.
Hudson
Lori L
LL
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425-2230, USA. hudsonll@musc.edu
Silver
Richard M
RM
Pandey
Janardan P
JP
D001741:Black or African American / Q000235:genetics*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000208:ethnology* / Q000235:genetics*; D044465:White People / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human