Lori L Hudson1, Richard M Silver, Janardan P Pandey. 1. Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425-2230, USA. hudsonll@musc.edu
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.
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.
Authors: G Balbi; F Ferrera; M Rizzi; P Piccioli; A Morabito; L Cardamone; M Ghio; G L Palmisano; P Carrara; S Pedemonte; M Sessarego; M De Angioletti; R Notaro; F Indiveri; M P Pistillo Journal: Clin Exp Immunol Date: 2007-04-25 Impact factor: 4.330
Authors: Nadia D Morgan; Ami A Shah; Maureen D Mayes; Robyn T Domsic; Thomas A Medsger; Virginia D Steen; John Varga; Mary Carns; Paula S Ramos; Richard M Silver; Elena Schiopu; Dinesh Khanna; Vivien Hsu; Jessica K Gordon; Heather Gladue; Lesley A Saketkoo; Lindsey A Criswell; Chris T Derk; Marcin A Trojanowski; Victoria K Shanmugam; Lorinda Chung; Antonia Valenzuela; Reem Jan; Avram Goldberg; Elaine F Remmers; Daniel L Kastner; Fredrick M Wigley; Pravitt Gourh; Francesco Boin Journal: Medicine (Baltimore) Date: 2017-12 Impact factor: 1.817