title: -295 T-to-C promoter region IL-16 gene polymorphism is associated with Whipple's disease.
abstract: Whipple's disease (WD) is a rare systemic condition caused, in genetically predisposed subjects, by Tropheryma whipplei, a common bacterium widespread in the environment. The relevance of genetic predisposition in WD is shown by the association with HLA alleles DRB1*13 and DQB1*06 and by the demonstration that, in patients with WD, the cytokine genetic profile is skewed toward a Th2 and Treg response. Since IL-16 is involved in hampering the development of a protective macrophagic response against Tropheryma whipplei, we investigated whether the genetic background of IL-16 is different between patients with WD and controls. The -295 T-to-C polymorphism of the promoter region of the IL-16 gene was studied in 90 patients with WD and 152 healthy controls. Levels of serum IL-16 protein were also tested. The frequency of the wild type T allele was significantly higher in patients with WD compared to the controls (155/180 vs. 235/304; p = 0.02 for the Chi(2) test), odds ratio 1.82 [95 % confidence interval (CI) 1.07-3.10]. The TT genotype was found in 65/90 patients with WD and 88/152 controls (p = 0.026). No relationship was found between serum levels of IL-16 and genotypes. Although the functional consequences of this genetic background on levels of IL-16 and on the course of the disease are still unknown, we found, for the first time, that the wild type T allele and the TT genotype of the -295 polymorphism are associated with WD.
authors.affiliation: First Department of Internal Medicine, IRCCS Foundation Policlinico San Matteo, University of Pavia, Pavia, Italy, f.biagi@smatteo.pv.it.
authors.forename: F
authors.initials: F
authors.lastname: Biagi
authors.forename: A
authors.initials: A
authors.lastname: Schiepatti
authors.forename: C
authors.initials: C
authors.lastname: Badulli
authors.forename: I
authors.initials: I
authors.lastname: Sbarsi
authors.forename: L
authors.initials: L
authors.lastname: Trotta
authors.forename: G E
authors.initials: GE
authors.lastname: Feurle
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: V
authors.initials: V
authors.lastname: Moos
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.forename: T
authors.initials: T
authors.lastname: Marth
authors.forename: M
authors.initials: M
authors.lastname: De Amici
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: G R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D019410:Interleukin-16 / Q000097:blood / Q000235:genetics*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D054851:Tropheryma / Q000276:immunology; D008061:Whipple Disease / Q000235:genetics* / Q000276:immunology / Q000382:microbiology
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C506473:HLA-DRB1*13 antigen; D019410:Interleukin-16