Review: Role of Genetics in Susceptibility and Outcome of Sarcoidosis

Johan Grunewald

doi:10.1055/s-0030-1262206

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2010; 31(4): 380-389
DOI: 10.1055/s-0030-1262206

Review: Role of Genetics in Susceptibility and Outcome of Sarcoidosis

Johan Grunewald¹ ^, ²

¹Department of Medicine, Division of Respiratory Medicine, Karolinska Institutet, Solna, Stockholm, Sweden
²Karolinska University Hospital, Solna, Stockholm, Sweden

Abstract

ABSTRACT

Sarcoidosis develops in genetically predisposed individuals that are exposed to unknown antigens. There is a statistically significant increased risk for the disease among family members of sarcoidosis patients, and the disease differs in different ethnic groups. It is a genetically complex disease, with many genes contributing, both as risk factors but also with an influence on the disease course. The strongest genetic associations with sarcoidosis are found within the major histocompatibility complex (MHC) [human leukocyte antigen (HLA) in humans]—region on chromosome six. This region includes, besides the HLA-class I and class-II genes, a large number of genes important for the immune response and inflammation. The well studied associations between sarcoidosis and HLA-class II molecules indicate specific antigen presentation for T helper cells, which is in agreement with the characteristic finding of lung-accumulated CD4+ T helper cells expressing a limited set of T cell receptors. Strong associations between distinct HLA-DRB1 alleles and the disease phenotype and course have been described, especially so in patient subgroups. Although a large number of genes are associated with sarcoidosis, this review focuses on gene associations and their influence on the disease phenotype, including the disease course.

KEYWORDS

Sarcoidosis - HLA - phenotype

Full Text

References

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Johan GrunewaldM.D.

Lung Research Laboratory L4:01

Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden

Email: johan.grunewald@ki.se