title: Variation in IL7R predisposes to sarcoid inflammation.
abstract: Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-alpha (IL7R alpha), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Löfgren's disease. The rs10213865 SNP was associated with sarcoidosis (P=0.008), and in silico analysis showed a complete linkage (r(2)=1, D'=1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P=5 x 10(-4), odds ratio=1.49 (1.19-1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Löfgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease.
authors.affiliation: Department of Pulmonology, Center for Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Heron
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: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
authors.forename: A M E
authors.initials: AM
authors.lastname: Claessen
authors.forename: J M M
authors.initials: JM
authors.lastname: van den Bosch
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium / Q000235:genetics; D008171:Lung Diseases / Q000235:genetics*; D008230:Lymphomatoid Granulomatosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D012507:Sarcoidosis / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D013577:Syndrome
chemical_list: D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain