title: Cystatin C is not a good candidate biomarker for HNF1A-MODY.
abstract: Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p < 0.05). Additionally, cystatin C-based GFR was higher than that calculated from creatinine level (p < 0.0001) in HNF1A-MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p < 0.0001). Concluding, we could not confirm our hypothesis (supported by the Polish results) that cystatin C level is altered by HNF1A mutations; thus, it cannot be used as a biomarker for HNF1A-MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one.
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Nowak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Szopa
authors.forename: Gaya
authors.initials: G
authors.lastname: Thanabalasingham
authors.forename: Tim J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: Kevin
authors.initials: K
authors.lastname: Colclough
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: James
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kozek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Katharine R
authors.initials: KR
authors.lastname: Owen
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000032:analysis; D055316:Cystatin C / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005919:Glomerular Filtration Rate; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D055316:Cystatin C; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D003404:Creatinine