title: Association of TNF, MBL, and VDR polymorphisms with leprosy phenotypes.
abstract: Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes, these findings have not been extensively validated. We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of seven polymorphisms, including a promoter region variant in TNF (G -308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI). We observed an association between TNF -308A and protection from leprosy with an odds ratio of 0.52 (95% confidence interval = 0.29-0.95, p = 0.016). MBL polymorphism G161A was associated with protection from lepromatous leprosy (odds ratio = 0.33, 95% confidence interval = 0.12-0.85, p = 0.010). VDR polymorphisms were not associated with leprosy phenotypes. These results confirm previous findings of an association of TNF -308A with protection from leprosy and MBL polymorphisms with protection from lepromatous leprosy. The statistical significance was modest and will require further study for conclusive validation.
authors.affiliation: Mycobacterial Research Laboratory, Anandaban Hospital, Kathmandu, Nepal.
authors.forename: Bishwa R
authors.initials: BR
authors.lastname: Sapkota
authors.forename: Murdo
authors.initials: M
authors.lastname: Macdonald
authors.forename: William R
authors.initials: WR
authors.lastname: Berrington
authors.forename: E Ann
authors.initials: EA
authors.lastname: Misch
authors.forename: Chaman
authors.initials: C
authors.lastname: Ranjit
authors.forename: M Ruby
authors.initials: MR
authors.lastname: Siddiqui
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D004893:Erythema Nodosum; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007918:Leprosy / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D009390:Nepal; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D037601:Mannose-Binding Lectin; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha