LARGE-SCALE CANDIDATE GENE STUDY OF LEPROSY SUSCEPTIBILITY IN THE KARONGA DISTRICT OF NORTHERN MALAWI

JODENE FITNESS Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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SIAN FLOYD Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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DAVID K. WARNDORFF Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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LIFTED SICHALI Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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LORREN MWAUNGULU Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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AMELIA C. CRAMPIN Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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PAUL E. M. FINE Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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ADRIAN V. S. HILL Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Tropical Hygiene, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Chilumba, Karonga District, Malawi

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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.

Author Notes

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