chitotriosidase activity and gene polymorphism in iranian patients with gaucher disease and sibling carriers

how to cite this article: mozafari h, taghikhani m, khatami sh, alaei mr, vaisi-raygani a, rahimi z. chitotriosidase activity and gene polymorphism in iranian patients with gaucher disease and sibling carriers. iran j child neurol. autumn 2016; 10(4):62-70. abstract objective chitotriosidase (ct) activity is a useful biomarker for diagnosis and monitoring of gaucher disease (gd). its application is limited by some variants in the ct gene. two main polymorphisms are 24 bp duplication and g102s led to reduce ct activity. the aim of this study was to determine these variants influencing on plasma ct activity.   materials & methods blood samples were collected from 33 patients with gd, 15 sibling carriers and 105 healthy individuals serving as controls. ct activity was measured using 4-methylumbelliferyl-β-d-n,n′,n″triacetylchitotrioside substrate in plasma samples. the ct genotypes of 24 bp duplication and g102s variants were determined using pcr and pcr-rflp.   results untreated gd patients had a significantly higher ct activity compared to treated patients (p = 0.021). in addition, chitotriosidase activity in carriers was higher rather than controls. allele frequencies of 24 bp duplication in gd patients, sibling carriers and controls were 0.21, 0.266 and 0.29 and for g102s were 0.318, 0.366 and 0.219, respectively. different g102s genotypes had not significant effect on ct activity. chitotriosidase activity has a positive correlation with age in normal group, carriers, and negative correlation with hemoglobin in gd patients. using cut-off level of 80.75 nmol/ml/h, sensitivity and specificity of ct activity were 93.9% and 100%, respectively.   conclusion chitotriosidase activity is a suitable biomarker for diagnosis and monitoring of gd. determination of 24 bp duplication is helpful for more accurate monitoring the gd patient’s therapy. however, it seems that, specifying of the g102s polymorphism is not required for iranian gd patients.   references 1. bennett ll, mohan d. gaucher disease and its treatment  options. ann pharmacother 2013;47(9):1182-93. 2. shrestha b, devgan a, sharma m. gaucher’s disease: rare presentation of a rare disease. j child neurol 2013;28(10):1296-8. 3. kanneganti m, kamba a, mizoguchi e. role of chitotriosidase (chitinase 1) under normal and disease conditions. j epithel biol pharmacol 2012;5:1-9. 4. adly aa, ismail ea, ibraheem tm. macrophagederived soluble cd163 level in young patients with gaucher disease: relation to phenotypes, disease severity and complications. int immunopharmacol 2015;24(2):416-22. 5. irún p, alfonso p, aznarez s, giraldo p, pocovi m. chitotriosidase variants in patients with gaucher disease.  implications for diagnosis and therapeutic monitoring. clin biochem 2013;46(18):1804-7. 6. grace me, balwani m, nazarenko i, prakash- cheng a, desnick rj. type 1 gaucher disease: null and hypomorphic novel chitotriosidase mutationsimplications for diagnosis and therapeutic monitoring. hum mutat 2007;28(9):866-73. 7. woo kh, lee bh, heo sh, kim jm, kim gh, kim ym, et al. allele frequency of a 24 bp duplication in exon 10 of the chit1 gene in the general korean population and in korean patients with gaucher disease. j hum genet 2014;59(5):276-9. 8. wajner a, michelin k, burin mg, pires rf, pereira ml, giugliani r, et al. comparison between the biochemical properties of plasma chitotriosidase from normal individuals and from patients with gaucher disease, gm1-gangliosidosis, krabbe disease and heterozygotes for gaucher disease. clin biochem 2007;40(5-6):365-9. 9. rosén c, andersson ch, andreasson u, molinuevo jl, bjerke m, rami l, et al. increased levels of chitotriosidase and ykl-40 in cerebrospinal fluid from patients with alzheimer’s disease. dement geriatr cogn dis extra 2014;31;4(2):297-304. 10. malaguarnera l. chitotriosidase: the yin and yang. cell mol life sci 2006;63(24):3018-29. 11. pagliardini v, pagliardini s, corrado l, lucenti a, panigati l, bersano e, et al. chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in myotrophic lateral sclerosis: a survey clinic-based study. j neurol sci 2015;15;348(1-2):245-50. 12. fusetti f, von moeller h, houston d, rozeboom hj, dijkstra bw, boot rg, et al. structure of human chitotriosidase. implications for specific inhibitor design and function of mammalian chitinase-like lectins. j biol chem 2002;277:25537–25544. 13. sista rs, wang t, wu n, graham c, eckhardt a, bali d, et al. rapid assays for gaucher and hurler diseases in dried blood spots using digital microfluidics. mol genet metab 2013;109(2): 218–220. 14. hollak ce, van weely s, van oers mh, aerts jm. marked elevation of plasma chitotriosidase activity. a novel hallmark of gaucher disease. j clin invest 1994;93(3):1288–1292. 15. old jm, higgs dr. gene analysis. in: weatherall dj, editor. methods in hematology. the thalassemias. vol. 6. london: churchill livingstone; 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