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Sarcoidosis and granuloma genes: a family-based study in African-Americans

¹ Dept of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan and ² Division of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai Medical Center, New York, New York, USA

CORRESPONDENCE: B.A. Rybicki, Dept of Biostatistics and Research Epidemiology, Henry Ford Health System, One Ford Place, 3E, Detroit, MI 48202, USA. Fax: 1 3138746730. E-mail: brybick1@hfhs.org

Keywords: Calcitriol receptor, genetic predisposition, peptidyl-dipeptidase A, polymorphism

Received: January 15, 2004
Accepted April 9, 2004

This study was supported by a National Institutes of Health grant R01 HL54306.

The evidence for a genetic component in the aetiology of sarcoidosis includes familial aggregation, associations with genetic polymorphisms, and linkage to the major histocompatibility complex class region on chromosome 6p. Unfortunately, the majority of genetic associations with sarcoidosis have not been consistently replicated.

In the present study, using a family-based study design, which controls for population stratification, the authors attempted to replicate previously reported associations between sarcoidosis and three attractive candidate genes studied primarily in case-control samples.

In 225 nuclear families, ascertained through African Americans with a history of sarcoidosis, no evidence was found for an association between sarcoidosis susceptibility and polymorphisms in the angiotensin converting enzyme, vitamin D receptor and tumour necrosis factor- genes. Further analyses of chronic and acute disease phenotypes failed to reveal any notable associations. Assuming an underlying inheritance model with an additive allelic effect on disease risk, the current study had 80–90% statistical power to detect a 3-fold increased risk associated with the putative risk allele of the polymorphisms under study.

The present authors conclude that in African-Americans, the angiotensin converting enzyme, vitamin D receptor, and tumour necrosis factor- genes are not significant risk factors for sarcoidosis susceptibility.

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