Sarcoidosis is a multisystem, granulomatous inflammatory disease of unknown etiology. Hereditary susceptibility to sarcoidosis is suggested by reports of familial clustering and a higher prevalence in certain ethnic groups, particularly African Americans. Over four hundred kindreds been reported in the medical literature and these investigators have recently described 101 families and shown that African Americans have a higher prevalence rate of familial sarcoidosis than Caucasians (19% vs. 5%). The reasons why sarcoidosis clusters in families or the role of genetic factors in this disease are not known. The objectives of this proposal are to determine if hereditary susceptibility predisposes African Americans to sarcoidosis and to identify sarcoidosis susceptibility genes in African Americans. The study will be carried out in African American families ascertained through 400 African American sarcoidosis patients evaluated at the Henry Ford Health System. They plan to test for association of sarcoidosis with markers for candidate genes using the affected family-based control method and test for possible environmental risk factors and genetic mechanisms of disease transmission by performing a segregation analysis in African American families. If one or more of the candidate genes studied show a strong association with sarcoidosis or if there is an indication of major gene segregation for the disease, they will be well positioned for future linkage studies. Investigating the hereditary susceptibility of sarcoidosis can best be done in African Americans, because of the greater severity and occurrence of disease in this population. Once the reasons for familial aggregation of sarcoidosis are determined, the investigators state that the etiology of this disease will be better understood and suitable prevention and treatment should be able to be designed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054306-03
Application #
2839016
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1996-12-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Levin, Albert M; Adrianto, Indra; Datta, Indrani et al. (2015) Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans. Am J Respir Cell Mol Biol 53:206-16
Li, Jia; Yang, James; Levin, Albert M et al. (2014) Efficient generalized least squares method for mixed population and family-based samples in genome-wide association studies. Genet Epidemiol 38:430-8
Levin, Albert M; Iannuzzi, Michael C; Montgomery, Courtney G et al. (2014) Admixture fine-mapping in African Americans implicates XAF1 as a possible sarcoidosis risk gene. PLoS One 9:e92646
Levin, Albert M; Adrianto, Indra; Datta, Indrani et al. (2014) Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, -DQB1, and -DPB1. BMC Genet 15:72
Adrianto, Indra; Lin, Chee Paul; Hale, Jessica J et al. (2012) Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. PLoS One 7:e43907
Rybicki, Benjamin A; Walewski, Jose L; Maliarik, Mary J et al. (2005) The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites. Am J Hum Genet 77:491-9
Rybicki, Benjamin A; Amend, Kandace L; Maliarik, Mary J et al. (2004) Photocopier exposure and risk of sarcoidosis in African-American sibs. Sarcoidosis Vasc Diffuse Lung Dis 21:49-55
Rybicki, B A; Maliarik, M J; Poisson, L M et al. (2004) Sarcoidosis and granuloma genes: a family-based study in African-Americans. Eur Respir J 24:251-7
Rybicki, Benjamin A; Maliarik, Mary J; Poisson, Laila M et al. (2003) The major histocompatibility complex gene region and sarcoidosis susceptibility in African Americans. Am J Respir Crit Care Med 167:444-9
Kucera, Gena P; Rybicki, Benjamin A; Kirkey, Kandace L et al. (2003) Occupational risk factors for sarcoidosis in African-American siblings. Chest 123:1527-35

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