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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2005

Open Access 01-12-2005 | Research article

Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study

Authors: Mirjam I Bakker, Linda May, Mochammad Hatta, Agnes Kwenang, Paul R Klatser, Linda Oskam, Jeanine J Houwing-Duistermaat

Published in: BMC Medical Genetics | Issue 1/2005

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Abstract

Background

It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but only few studies have tempted to quantify this. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often share the same environment. The first aim of this study was to test which correlation structure (genetic, household or spatial) gives the best explanation for the distribution of leprosy patients and seropositive persons and second to quantify the role of genetic factors in the occurrence of leprosy and seropositivity.

Methods

The three correlation structures were proposed for population data (n = 560), collected on a geographically isolated island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and persons harbouring Mycobacterium leprae-specific antibodies. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M. leprae antibodies were measured using ELISA.

Results

For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the spatial model, but the genetic model was also significant. Heritability was 57% for leprosy per se and 31% for seropositivity.

Conclusion

Genetic factors seem to play an important role in the clustering of patients with a more advanced form of leprosy, and they could explain more than half of the total phenotypic variance.
Appendix
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Literature
1.
World Health Organization: Leprosy – Global situation. Wkly Epidemiol Rec. 2002, 1: 1-8.
2.
3.
Bagshawe A, Burgh de S, Fung SC, Chuah J, Berry G: The epidemiology of leprosy in a high prevalence village in Papua New Guinea. Trans R Soc Trop Med Hyg. 1989, 89: 121-127. 10.1016/0035-9203(89)90735-9.CrossRef
4.
Fine PE, Sterne JA, Ponnighaus JM, Bliss L, Saui J, Chihana A, Munthali M, Warndorff DK: Household and dwelling contact as risk factors for leprosy in Northern Malawi. Am J Epidemiol. 1997, 146: 91-102.CrossRefPubMed
5.
Van Beers SM, Hatta M, Klatser PR: Patient contact is the major determinant in incident leprosy: implication for future control. Int J Lepr Other Mycobact Dis. 1999, 67: 119-128.PubMed
6.
Bakker MI, Hatta M, Kwenang A, Klatser PR, Oskam L: Epidemiology of leprosy of five isolated islands in the Flores Sea, Indonesia. Trop Med Int Health. 2002, 7: 780-787. 10.1046/j.1365-3156.2002.00931.x.CrossRefPubMed
7.
Siddiqui MR, Meisner S, Tosh K, Balaksishnan K, Ghei S, Fisher SE, Golding M, Narayan NPS, Sitaraman T, Sengupta U, Pitchappan R, Hill AVS: A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat genet. 2001, 27: 439-441. 10.1038/86958.CrossRefPubMed
8.
Tosh K, Meisner S, Siddiqui MR, Balakrishnan K, Ghei S, Golding M, Sengupta U, Pitchappan RM, Hill AVS: A region of chromosome 20 is linked to leprosy susceptibility in a South Indian population. J Infect Dis. 2002, 186: 1190-1193. 10.1086/343806.CrossRefPubMed
9.
Mira MT, Alcais A, Nguyen VT, Moraes MO, Di Flumeri C, Vu HT, Mai CP, Nguyen TH, Nguyen NB, Pham XK, Sarno EN, Alter A, Montpetit A, Moraes ME, Moraes JR, Dore C, Gallant CJ, Lepage P, Verner A, Van De Vosse E, Hudson TJ, Abel L, Schurr E: Susceptibility to leprosy is associated with PARK2 and PACRG. Nature. 2004, 427: 636-640. 10.1038/nature02326.CrossRefPubMed
10.
Wagener DK, Schauf V, Nelson KE, Scollard D, Brown A, Smith T: Segregation analysis of leprosy in families of northern Thailand. Genet Epidemiol. 1988, 5: 95-105. 10.1002/gepi.1370050205.CrossRefPubMed
11.
Abel L, Vu DL, Oberti J, Nguyen VT, Van VC, Guilloud-Bataille M, Schurr E, Lagrange PH: Complex segregation analysis of leprosy in southern Vietnam. Genet Epidemiol. 1995, 12: 63-82. 10.1002/gepi.1370120107.CrossRefPubMed
12.
Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV: Association of vitamin D receptor genotype with leprosy type. J Infect Dis. 1999, 179: 187-191. 10.1086/314536.CrossRefPubMed
13.
Shaw MA, Donaldson IJ, Collins A, Peacock CS, Lins-Lainson Z, Shaw JJ, Ramos F, Silveira F, Blackwell JM: Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes. Genes Immun. 2001, 2: 196-204. 10.1038/sj.gene.6363754.CrossRefPubMed
14.
Casanova JL, Abel L: Genetic Dissection of Immunity to Mycobacteria: the human model. Annu Rev Immunol. 2002, 20: 581-620. 10.1146/annurev.immunol.20.081501.125851.CrossRefPubMed
15.
Fitness J, Tosh H, Hill AVS: Genetics of susceptibility to leprosy. Genes Immun. 2002, 3: 441-453. 10.1038/sj.gene.6363926.CrossRefPubMed
16.
17.
Mira MT, Alcaïs A, Thuc NV, Tahi VH, Huong NT, Ba NN, Verner A, Hudson TJ, Abel L, Schurr E: Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet. 2003, 33: 412-415. 10.1038/ng1096.CrossRefPubMed
18.
Wallace C, Clayton D, Fine P: Estimating the relative recurrence risk ratio for leprosy in Karonga District, Malawi. Lepr Rev. 2003, 74: 133-140.PubMed
19.
Douglas JT, Cellona RV, Fajardo TT, Abalos RM, Balagon MVF, Klatser PR: Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol. 2004, 11: 897-900. 10.1128/CDLI.11.5.897-900.2004.PubMedPubMedCentral
20.
Thompson EA: Pedigree Analysis in Human Genetics. 1986, Baltimore: Johns Hopkins University Press
21.
Bührer-Sékula S, Sarno EN, Oskam L, Koop S, Wichers I, Nery JA, Vieira LM, de Matos HJ, Faber WR, Klatser PR: Use of ML dipstick as a tool to classify leprosy patients. Int J Lepr Other Mycobact Dis. 2000, 68: 456-463.PubMed
22.
Fine PEM, Ponnighaus JM, Burgess P, Clarkson JA, Draper CC: Seroepidemiological studies of leprosy in Northern Malawi on an enzyme-linked immunosorbent assay using synthetic glycoconjugate antigen. Int J Lepr Other Mycobact Dis. 1988, 56: 243-254.PubMed
23.
Houwing-Duistermaat JJ, Derkx BH, Rosendaal FR, van Houwelingen HC: Testing familial aggregation. Biometrics. 1995, 51: 1292-1301.CrossRefPubMed
24.
Altman DG: Practical statistics for medical research. 1991, London: Chapman & Hall
25.
Houwing-Duistermaat JJ, van Houwelingen HC, de Winter JP: Estimation of individual genetic effects from binary observations on relatives applied to a family history of respiratory illnesses and chronic lung disease of newborns. Biometrics. 2000, 56: 808-814. 10.1111/j.0006-341X.2000.00808.x.CrossRefPubMed
26.
Olson JM, Cordell HJ: Ascertainment bias in the estimation of sibling genetic risk parameters. Genet Epidemiol. 2000, 18: 217-235. 10.1002/(SICI)1098-2272(200003)18:3<217::AID-GEPI3>3.0.CO;2-8.CrossRefPubMed
27.
Zou G, Zhao H: The estimation of sibling genetic risk parameters revisited. Genet Epidemiol. 2004, 26: 286-293. 10.1002/gepi.10322.CrossRefPubMed
28.
Houwing-Duistermaat JJ, Van Houwelingen HC, Terhell A: Modelling the cause of dependency with application to filaria infection. Stat Med. 1998, 17: 2939-2954. 10.1002/(SICI)1097-0258(19981230)17:24<2939::AID-SIM904>3.3.CO;2-L.CrossRefPubMed
29.
Noordeen SK: The epidemiology of leprosy. Leprosy. Edited by: Hastings. 1985, London: Churchill Livingstone, 15-30.
30.
31.
Segal S, Hill AV: Genetic susceptibility to infectious disease. Trends Microbiol. 2003, 11: 445-448. 10.1016/S0966-842X(03)00207-5.CrossRefPubMed
32.
Smith DG: The genetic hypothesis for susceptibility to lepromatous leprosy. Hum Genet. 1979, 50: 163-177. 10.1007/BF00390238.CrossRefPubMed
33.
Bakker MI, Hatta M, Kwenang A, Faber WR, Van Beers SM, Klatser PR, Oskam L: Population survey to determine risk factors for Mycobacterium leprae transmission and infection. Int J Epidemiol. 2004, 33: 1329-1336. 10.1093/ije/dyh266.CrossRefPubMed
Metadata
Title
Genetic, household and spatial clustering of leprosy on an island in Indonesia: a population-based study
Authors
Mirjam I Bakker
Linda May
Mochammad Hatta
Agnes Kwenang
Paul R Klatser
Linda Oskam
Jeanine J Houwing-Duistermaat
Publication date
01-12-2005
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2005
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-6-40

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