title: Association of chitotriosidase enzyme activity and genotype with the risk of nephropathy in type 2 diabetes.
abstract: OBJECTIVE
  The immune-inflammatory system has been implicated in the pathogenesis of diabetic nephropathy; however, many of the mechanisms involved remain unclear. Chitotriosidase enzyme is an active human chitinase and a major protein product of activated macrophages. Although playing an important role in innate and acquired immunity, chitotriosidase involvement in the development of diabetic nephropathy is unknown.
  
  
  METHODS
  Chitotriosidase enzyme activity and the presence of the functional 24-bp duplication mutation of the chitotriosidase gene (CHIT1) were assessed in 262 Egyptian type 2 diabetic patients with and without nephropathy and 90 non-diabetic controls. In diabetic patients, multiple linear regression models were adapted to assess the association of chitotriosidase activity with two important measures of renal disease progression: urinary albumin/creatinine ratio and eGFR, while the association of the CHIT1 genotype with the incidence of nephropathy was evaluated by multiple logistic regression.
  
  
  RESULTS
  In diabetic patients, chitotriosidase enzyme activity showed a statistically significant elevation as compared to controls and correlated positively with the progression of nephropathy. A significant association of chitotriosidase activity with both urinary albumin/creatinine ratio and eGFR was detected after adjusting for age, gender, duration of diabetes, body mass index, hypertension status, total cholesterol, triglycerides and HbA1c levels, P<0.001. We also identified a protective association between the CHIT1 mutated genotype and diabetic nephropathy after adjusting for the same confounders (odds ratio: 0.517, 95% CI: 0.289-0.924, P=0.026).
  
  
  CONCLUSIONS
  This study demonstrates for the first time that the immunomodulatory effects of chitotriosidase enzyme could be implicated in the development of nephropathy in type 2 diabetes.
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt. Electronic address: mohamed.abdelmonem@kasralainy.edu.eg.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Elmonem
authors.affiliation: Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt.
authors.forename: Hanan S
authors.initials: HS
authors.lastname: Amin
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Riham A
authors.initials: RA
authors.lastname: El-Essawy
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Dina A
authors.initials: DA
authors.lastname: Mehaney
authors.affiliation: Department of Nephrology, Theodor Bilharz Research Institute, Giza, Egypt.
authors.forename: Malak
authors.initials: M
authors.lastname: Nabil
authors.affiliation: Department of Clinical Chemistry, Theodor Bilharz Research Institute, Giza, Egypt.
authors.forename: Laila N
authors.initials: LN
authors.lastname: Kamel
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Ibtisam M
authors.initials: IM
authors.lastname: Farid
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D006596:Hexosaminidases / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D006596:Hexosaminidases; C086400:chitotriosidase
keywords: 24-bp duplication; CHIT1 genotype; Chitotriosidase; Diabetic nephropathy; Type 2 diabetes