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

• Published in: The European respiratory journal Vol. 24; no. 2; pp. 251 - 257
• Main Authors: Rybicki, B.A, Maliarik, M.J, Poisson, L.M, Iannuzzi, M.C
• Format: Journal Article
• Language: English
• Published: Leeds Eur Respiratory Soc 01-08-2004; Maney
• Subjects: African Americans - genetics; Alleles; Biological and medical sciences; Case-Control Studies; Chi-Square Distribution; Female; Genetic Predisposition to Disease - epidemiology; Genotype; Humans; Incidence; Lung Diseases - ethnology; Lung Diseases - genetics; Male; Medical sciences; Pedigree; Peptidyl-Dipeptidase A - genetics; Pneumology; Polymorphism, Genetic; Probability; Receptors, Calcitriol - genetics; Risk Assessment; Sarcoidosis - ethnology; Sarcoidosis - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sensitivity and Specificity; Tumor Necrosis Factor-alpha - genetics; United States - epidemiology; United States; Granuloma; Gene; Sarcoidosis; Family study; Calcitriol receptor genetic predisposition peptidyl-dipeptidase A polymorphism; Systemic disease; African American
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.04.00005904

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-alpha 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 approximately 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-alpha genes are not significant risk factors for sarcoidosis susceptibility.