September 1, 2001American Journal of Respiratory and Critical Care Medicine196 citations
View Full PaperResults from a Genome-wide Search for Predisposing Genes in Sarcoidosis
Structured PICO
P
Population
63 families with affected siblings (138 patients) with sarcoidosis
I
Intervention
Genome-wide microsatellite linkage analysis using 225 microsatellite markers
O
Outcome
Chromosomal regions contributing to the risk of sarcoidosissurrogate
Genome-wide linkage analysis identifies the major histocompatibility complex as a major susceptibility locus for sarcoidosis, alongside locus heterogeneity.
Abstract
Sarcoidosis is a systemic disease of granulomatous inflammation and unknown etiology. An inherited predisposition is involved, and many candidate susceptibility genes have been tested in association studies. We have applied the more general strategy of genome-wide microsatellite linkage analysis to identify chromosomal regions that contribute to the risk of sarcoidosis. On the basis of 225 microsatellite markers tested in 63 families with affected siblings (138 patients) and multipoint nonparametric linkage (NPL) analysis, we found the most prominent peak (six adjacent markers including D6S1666; NPL score = 2.99; p = 0.001) at the major histocompatibility complex (MHC). Six minor peaks (p < 0.05) were found on chromosomes 1 (D1S1665 ), 3 (D3S1766 ), 7 (D7S821 and D7S3070), 9 (D9S934), and the X chromosome (DXS6789). A subset of nine families with more than two affected siblings (30 patients) contributed little to the peak at the MHC (D6S1666; NPL score = 0.79; p = 0.21). Our results point to locus heterogeneity of susceptibility to sarcoidosis, with a major effect of the MHC.