title: PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever.
abstract: Host genetic factors may contribute to susceptibility to and outcome in infectious diseases. Recently polymorphisms in PARK2/PACRG, a gene cluster linked to ubiquitination and proteasome-mediated protein degradation, were found to be associated with manifest infection by M. leprae. Here, we address whether these polymorphisms are associated with susceptibility to infection with Salmonella typhi and S. paratyphi A, intracellular pathogens that upon infection of humans share with mycobacteria aspects of the hosts' immune response. The polymorphisms of PARK_e01(-697), PARK2_e01(-2599), rs1333955 and rs1040079 were analysed by polymerase chain reaction and restriction fragment length polymorphism in a case-control study of typhoid and paratyphoid fever patients in an endemic area in Jakarta, Indonesia. For this study, samples were obtained from patients with blood culture-confirmed typhoid fever (n=90), paratyphoid fever (n=26) and fever controls (n=337) in a passive, community-based surveillance and compared to those of randomly selected community controls (n=322) from the same city area. The PARK2_e01(-2599) allele T was significantly associated with typhoid and paratyphoid fever (OR: 1.51, 95%CI: 1.02-2.23) but the other polymorphisms, PARK2_e01(-697), rs1333955 and rs1040079, were not associated. Although within the PARK2/PACRG gene cluster the PARK2_e01(-2599) allele T was most strongly associated with leprosy (OR approximately 3-5), the association with typhoid is much less strong. Our findings suggest that this polymorphism in PARK2/PACRG plays a small but significant role in susceptibility to the intracellular pathogens S. typhi and S. paratyphi.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Centre, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Ali
authors.forename: A M
authors.initials: AM
authors.lastname: Vollaard
authors.forename: S
authors.initials: S
authors.lastname: Widjaja
authors.forename: C
authors.initials: C
authors.lastname: Surjadi
authors.forename: E
authors.initials: E
authors.lastname: van de Vosse
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D018832:Molecular Chaperones / Q000235:genetics*; D010284:Paratyphoid Fever / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014435:Typhoid Fever / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D008840:Microfilament Proteins; D018832:Molecular Chaperones; C471711:PACRG protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein