Familial sarcoidosis is linked to the major histocompatibility complex region

Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):861-4. doi: 10.1164/ajrccm.162.3.9901099.


Sarcoidosis is a systemic granulomatous disorder associated with high CD4+ cell activity, but no pathogen is detectable. Clustering in families occurs, and the existence of a genetic predisposition to sarcoidosis is widely accepted. The major histocompatibility complex (MHC) is believed to contribute to this susceptibility. Many studies testing this hypothesis have produced conflicting results. We have genotyped 122 affected siblings from 55 families for seven DNA polymorphisms that flank and cover the MHC region on chromosome 6, and for HLA-DPB1, a candidate gene for granulomatous disorders. Multipoint nonparametric linkage (NPL) analysis showed linkage (NPL score > 2.5; p < 0.006) for the entire MHC region with a maximum NPL score of 3.2 (p = 0.0008) at marker locus D6S1666 in the Class III gene cluster. There was a significant excess of marker haplotype sharing among affected siblings. However, the frequency of HLA-DPB1 alleles on 104 shared chromosomes did not differ from that of a control group of founders from the family panel. Transmission disequilibrium was found for allele DPB1*0201, but only nine families contributed to this result. We conclude that genes of the MHC are involved in the genetic predisposition to sarcoidosis, but HLA-DPB1 alone does not sufficiently explain this fact.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 6
  • Female
  • Gene Frequency
  • Genetic Linkage / genetics*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • HLA-DP Antigens / genetics
  • HLA-DP beta-Chains
  • Humans
  • Major Histocompatibility Complex / genetics*
  • Male
  • Sarcoidosis / diagnosis
  • Sarcoidosis / genetics*


  • Genetic Markers
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen