title: Polymorphisms in catechol-O-methyltransferase and cytochrome p450 subfamily 19 genes predispose towards Madurella mycetomatis-induced mycetoma susceptibility.
abstract: Mycetoma caused by Madurella mycetomatis is a devastating and neglected disease which primarily affects males. Since this predominance cannot be easily explained by behaviour differences between men and women, other factors, including sex hormones, could be the cause. To monitor for possible deficiencies in hormone synthesis among mycetoma patients, we investigated the types and allele frequencies of the genes encoding for catechol-O-methyltransferase (COMT), cytochrome p450 subfamily 1 (CYP1B1), cytochrome p450 subfamily 17 (CYP17), cytochrome p450 subfamily 19 (CYP19) and hydroxysteroid dehydrogenase 3B (HSD3B). Significant differences in allele distribution were demonstrated for CYP19 (P=0.004) and COMT (P=0.005), as well as gender dimorphism for both CYP19 and COMT polymorphisms. The COMT polymorphism was associated with lesion size. The genotypes obtained for COMT and CYP19 were connected with higher 17&#x03B2;-estradiol production, which was confirmed by significantly elevated serum levels of 17&#x03B2;-estradiol in male patients. In contrast, lowered levels of dehydroepiandrosteron (DHEA) were found in mycetoma patients. The in vitro growth of M. mycetomatis was not influenced by 17&#x03B2;-estradiol, progesterone, DHEA and testosterone. The differences in hormone levels we noted between mycetoma patients and healthy controls did not directly affect the fungus itself. Indirect effects on the patients' hormone regulated immune states are the more likely explanations for mycetoma susceptibility.
authors.affiliation: Erasmus MC, University Medical Centre Rotterdam, Department of Medical Microbiology & Infectious Diseases, Rotterdam, The Netherlands. w.vandesande@erasmusmc.nl
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: van de Sande
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fahal
authors.forename: Mehri
authors.initials: M
authors.lastname: Tavakol
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D020461:Madurella; D008297:Male; D008875:Middle Aged; D008271:Mycetoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013397:Sudan
chemical_list: D001141:Aromatase; D002394:Catechol O-Methyltransferase