title: Toll-like receptor (TLR) 4 polymorphism Asp299Gly is not associated with disease course in Dutch sarcoidosis patients.
abstract: The aetiology of sarcoidosis, a systemic disorder characterized by the formation of non-caseating granulomas in variable organs, remains enigmatic. Clarification is hampered by heterogeneity in disease phenotypes and course, due partly to the influence of a variety of genetic and environmental factors. Multiple studies have pointed towards bacteria as possible causative agents. Toll-like receptors (TLR) are innate immunity receptors important in the immune response against pathogens. TLR-4, together with CD14 and MD-2, is an essential receptor for the recognition of lipopolysaccharide (LPS), unique to the cell wall of Gram-negative bacteria. Recently, an association between TLR-4 polymorphism Asp299Gly, leading to a change in the extracellular domain of the receptor and possible hyporesponsiveness to LPS, and a chronic course of sarcoidosis was found in German patients. In the present study this polymorphism was genotyped in 156 Dutch sarcoidosis patients and 200 healthy Dutch controls using dual-labelled fluorescent oligonucleotides. No differences were found in allelic distributions between patients and controls (P = 0.79) or within the different clinical entities of the sarcoidosis group (P = 0.44). Importantly, there were no differences between the Dutch and German sarcoidosis patients (P = 0.62). However, the allelic distribution of the Asp299Gly polymorphism differed significantly between both control groups (P = 0.04). This study highlights the importance of testing a reported gene association in a distinct population when performing genetic association studies.
authors.affiliation: Heart Lung Centre Utrecht, the Netherlands. m.veltkamp@antonius.net
authors.forename: M
authors.initials: M
authors.lastname: Veltkamp
authors.forename: J C
authors.initials: JC
authors.lastname: Grutters
authors.forename: C H M
authors.initials: CH
authors.lastname: van Moorsel
authors.forename: H J T
authors.initials: HJ
authors.lastname: Ruven
authors.forename: J M M
authors.initials: JM
authors.lastname: van den Bosch
mesh_terms: D000208:Acute Disease; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002908:Chronic Disease; D018450:Disease Progression; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009426:Netherlands; D011110:Polymorphism, Genetic; D015995:Prevalence; D017565:Sarcoidosis, Pulmonary / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051197:Toll-Like Receptor 4