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TCRBV20S1 and TCRBV3S1 Gene Segment Polymorphisms in Systemic Sclerosis

MARKUS BREDEMEIER, JOSÉ ARTUR BOGO CHIES, ANDRÉA WIECK, KARINA GATZ CAPOBIANCO, EDUARDO HENNEMANN PITREZ, LUIS EDUARDO PAIM ROHDE, ANTÔNIO FERNANDO FURLAN PINOTTI, JOÃO CARLOS TAVARES BRENOL, and RICARDO MACHADO XAVIER

ABSTRACT.

Objective. To compare the frequencies of variants of TCRBV20S1 and TCRBV3S1 gene segments in patients with systemic sclerosis (SSc) and in controls. The null allele (allele 2) of TCRBV20S1 is associated with reduced levels of Vß20+ T-cells in the peripheral blood, while allele 1 of TCRBV3S1 is related to a low frequency of Vß3.1+ T-cells.

Methods. One hundred thirty patients with SSc and 118 healthy volunteer controls were genotyped for TCRBV20S1, and 117 patients and 85 controls were genotyped for TCRBV3S1 variants by PCR-RFLP. Patients underwent clinical evaluation, serology, pulmonary function tests, high resolution computed tomography, and Doppler echocardiography.

Results. The genotypic frequencies of TCRBV20S1 were 0.46 (allele 1/allele 1), 0.43 (allele 1/allele 2), and 0.11 (allele 2/allele 2) in SSc patients; in controls the frequencies were 0.70, 0.26, and 0.04, respectively (p < 0.001). The Mantel-Haenszel odds ratio (stratified by race and sex) of the allele 2 carrier state was 3.88 (95% CI 1.94 to 7.75). The allelic and genotypic frequencies of the TCRBV3S1 gene segment did not differ significantly in patients and controls. However, among patients, allele 1 (TCRBV3S1) carriers had a higher prevalence of interstitial lung disease (adjusted p = 0.032).

Conclusion. The null allele of the TCRBV20S1 and the allele 1 of TCRBV3S1 gene segments may be considered risk factors for the development of SSc and interstitial lung disease, respectively, suggesting a protective role of Vß20+ and Vß3.1+ cells in the pathogenic immune responses in SSc. (J Rheumatol First Release April 15 2008)

Key Indexing Terms:

SYSTEMIC SCLERODERMA
T-CELL RECEPTOR BETA GENES
SINGLE-NUCLEOTIDE POLYMORPHISM
CASE-CONTROL STUDY

From the Divisions of Rheumatology, Radiology, and Cardiology of the Hospital de Clínicas de Porto Alegre and from the Genetics Department of the Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Supported in part by grants from Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre (FIPE/HCPA).

M. Bredemeier, MD, PhD, Division of Rheumatology, Hospital de Clínicas de Porto Alegre; J.A.B. Chies, PhD, Adjunct Professor; A. Wieck, MSc, Genetics Department, Universidade Federal do Rio Grande do Sul; K.G. Capobianco, MD, PhD, Division of Rheumatology; E.H. Pitrez, MD, PhD, Division of Radiology; L.E.P. Rohde, MD, PhD; A.F.F. Pinotti, MD, MSc, Division of Cardiology; J.C.T. Brenol, MD, PhD, Associate Professor of Rheumatology; R.M. Xavier, MD, PhD, Divison of Rheumatology, Hospital de Clínicas de Porto Alegre, Associate Professor of Rheumatology, Universidade Federal do Rio Grande do Sul.

Address reprint requests to Dr. M. Bredemeier, Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350/ sala 645, Porto Alegre, RS, 90035-003, Brazil. E-mail: markbred@terra.com.br

Accepted for publication January 23, 2008.