title: Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.
abstract: Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.
authors.affiliation: Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands. y.stienstra@int.umcg.nl
authors.forename: Y
authors.initials: Y
authors.lastname: Stienstra
authors.forename: T S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: E
authors.initials: E
authors.lastname: Oosterom
authors.forename: I M
authors.initials: IM
authors.lastname: Nolte
authors.forename: W T A
authors.initials: WT
authors.lastname: van der Graaf
authors.forename: S
authors.initials: S
authors.lastname: Etuaful
authors.forename: P L
authors.initials: PL
authors.lastname: Raghunathan
authors.forename: E A S
authors.initials: EA
authors.lastname: Whitney
authors.forename: E O
authors.initials: EO
authors.lastname: Ampadu
authors.forename: K
authors.initials: K
authors.lastname: Asamoa
authors.forename: E Y
authors.initials: EY
authors.lastname: Klutse
authors.forename: G J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: J W
authors.initials: JW
authors.lastname: Tappero
authors.forename: D A
authors.initials: DA
authors.lastname: Ashford
authors.forename: G
authors.initials: G
authors.lastname: van der Steege
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001216:Asparagine / Q000737:chemistry / Q000235:genetics; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009165:Mycobacterium Infections, Nontuberculous / Q000150:complications / Q000235:genetics*; D019911:Mycobacterium ulcerans; D011110:Polymorphism, Genetic; D012883:Skin Ulcer / Q000235:genetics* / Q000382:microbiology*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001216:Asparagine; D001224:Aspartic Acid; D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1