A Polymorphism in the Chitotriosidase Gene Associated with Risk of Mycetoma Due to Madurella mycetomatis Mycetoma--A Retrospective Study.
BACKGROUND
Madurella mycetomatis is the most prevalent causative agent of eumycetoma in Sudan, an infection characterized by the formation of grains. Many patients are exposed to the causative agent, however only a small number develop infection. M. mycetomatis contains chitin in its cell wall, which can trigger the human immune system. Polymorphisms in the genes encoding for the chitin-degrading enzymes chitotriosidase and AMCase were described, resulting in altered chitinase activity. We investigated the association between 4 of these polymorphisms and the incidence of M. mycetomatis mycetoma in a Sudanese population.


METHODS
Polymorphisms studied in 112 eumycetoma patients and 103 matched controls included a 24-bp insertion in the chitotriosidase gene (rs3831317), resulting in impaired chitinase activity and single nucleotide polymorphism (SNP) in the AMCase gene (rs61756687), resulting in decreased AMCase activity. Also, a SNP (rs41282492) and a 10-bp insertion in the 5'UTR region of the AMCase gene (rs143789088) were studied, both resulting in increased AMCase activity. DNA was isolated from blood and genotypes were determined using PCR-RFLP.


RESULTS
Histological staining proved the presence of chitin in the fungal grain. The polymorphism resulting in decreased chitotriosidase activity was associated with increased odds of eumycetoma (odds ratio 2.9; p = 0.004). No association was found for the polymorphisms in the genes for AMCase (all p>0.05).


CONCLUSIONS
Decreased chitotriosidase activity was associated with increased risk of M. mycetomatis mycetoma.
Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, CE Rotterdam, The Netherlands.
Patricia E B
PE
Verwer
Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, CE Rotterdam, The Netherlands.
Charlotte C
CC
Notenboom
Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, CE Rotterdam, The Netherlands.
Kimberly
K
Eadie
Mycetoma Research Centre, Khartoum, Sudan.
Ahmed H
AH
Fahal
Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, CE Rotterdam, The Netherlands.
Henri A
HA
Verbrugh
Dept. of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, CE Rotterdam, The Netherlands.
Wendy W J
WW
van de Sande
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006596:Hexosaminidases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D020461:Madurella / Q000302:isolation & purification*; D008297:Male; D008271:Mycetoma / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology*; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018570:Risk Assessment; D013397:Sudan / Q000453:epidemiology; D055815:Young Adult
D006596:Hexosaminidases; C086400:chitotriosidase