title: Large-scale candidate gene study of leprosy susceptibility in the Karonga district of northern Malawi.
abstract: We present a large case-control candidate gene study of leprosy susceptibility. Thirty-eight polymorphic sites from 13 genes were investigated for their role in susceptibility to leprosy by comparing 270 cases with 452 controls in Karonga district, northern Malawi. Homozygotes for a silent T-->C change in codon 352 of the vitamin D receptor gene appeared to be at high risk (odds ratio [OR] = 4.3, 95% confidence interval [CI] = 1.6-11.4, P = 0.004), while homozygotes for the McCoy b blood group defining variant K1590E in exon 29 of the complement receptor 1 (formerly CD35) gene appeared to be protected (OR = 0.3, 95% CI = 0.1-0.8, P = 0.02). Borderline evidence for association with leprosy susceptibility was found for seven polymorphic sites in an additional six genes. Some of these apparent associations may be false-positive results from multiple comparisons, and several associations suggested by studies in other populations were not replicated here. These data provide evidence of inter-population heterogeneity in leprosy susceptibility.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. jodene.fitness@vuw.ac.nz
authors.forename: Jodene
authors.initials: J
authors.lastname: Fitness
authors.forename: Sian
authors.initials: S
authors.lastname: Floyd
authors.forename: David K
authors.initials: DK
authors.lastname: Warndorff
authors.forename: Lifted
authors.initials: L
authors.lastname: Sichali
authors.forename: Lorren
authors.initials: L
authors.lastname: Mwaungulu
authors.forename: Amelia C
authors.initials: AC
authors.lastname: Crampin
authors.forename: Paul E M
authors.initials: PE
authors.lastname: Fine
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D008295:Malawi; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA