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Published ahead of print on February 13, 2003, doi:10.1164/rccm.200209-1097OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 9, May 2003, 1225-1231

A more recent version of this article appeared on May 1, 2003
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Submitted on October 1, 2002
Accepted on January 31, 2003

Sarcoidosis susceptibility and resistance HLA DQB1 alleles in African Americans

Michael C Iannuzzi1*, Mary J Maliarik2, Laila M Poisson3, and Benjamin A Rybicki3

1 Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, New York, NY, USA, 2 Pulmonary, Critical Care, Allergy and Sleep Medicine, Henry Ford Health System, Detroit, MI, USA, 3 Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, MI, USA

* To whom correspondence should be addressed. E-mail: miannuz1{at}hfhs.org.

Sarcoidosis, in the US, more commonly and severely affects African Americans. HLA associations with sarcoidosis have been reported, but most studies used case control designs which may produce biased results due to population stratification. We examined transmission of HLA-DQB1 alleles in 225 African American families with at least one offspring with sarcoidosis. Of five low resolution DQB1 alleles, *02 and *06, showed significant deviation in transmission patterns to affected offspring. High resolution typing of these allelic subsets revealed that HLA-DQB1*0201 was transmitted to affected offspring half as often as expected (P = 0.001), whereas DQB1*0602 was transmitted to affected offspring about 20% more often than expected (dominant model P=0.052; additive model P=0.029). Examining interactions between *0201 and *0602 alleles and environmental exposures showed that *0602 varied little with respect to exposure, but sarcoidosis risk associated with *0201 depended upon exposure status. In addition, the *0602 allele in affected probands was associated with radiographic disease progression, but the *0201 allele showed no significant correlation with phenotype. Major differences in the amino acid sequence of *0201 and *0602 alleles exist that may explain the differential effects these alleles have on sarcoidosis susceptibility and progression in African Americans.
Key words: Sarcoidosis, HLA antigens, Blacks, Disease susceptibility, Genetic predisposition




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