Carnosinase concentration, activity, and CNDP1 genotype in patients with type 2 diabetes with and without nephropathy

被引:15
作者
Zhang, Shiqi [1 ,2 ]
Albrecht, Thomas [1 ]
Rodriguez-Nino, Angelica [1 ]
Qiu, Jiedong [1 ]
Schnuelle, Peter [1 ]
Peters, Verena [3 ]
Schmitt, Claus Peter [3 ]
van den Born, Jacob [4 ]
Bakker, Stephan J. L. [4 ]
Lammert, Alexander [1 ]
Kraemer, Bernhard K. [1 ]
Yard, Benito A. [1 ]
Hauske, Sibylle J. [1 ]
机构
[1] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Med Nephrol Endocrinol Rheumatol 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany
[2] Anhui Med Univ, Affiliated Hosp 1, Dept Endocrinol, Hefei, Anhui, Peoples R China
[3] Heidelberg Univ, Ctr Pediat & Adolescent Med, Heidelberg, Germany
[4] Univ Groningen, Univ Med Ctr Groningen, Nephrol, Groningen, Netherlands
关键词
Diabetes; Nephropathy; Carnosinase; Dialysis; LEUCINE REPEAT; GENE CNDP1; ASSOCIATION; RISK; POLYMORPHISM; RETINOPATHY;
D O I
10.1007/s00726-018-02692-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study assessed if serum carnosinase (CNDP1) activity and concentration in patients with type 2 diabetes mellitus (T2D) with diabetic nephropathy (DN) differs from those without nephropathy. In a cross-sectional design 127 patients with T2D with DN ((CTG)(5) homozygous patients n=45) and 145 patients with T2D without nephropathy ((CTG)(5) homozygous patients n=47) were recruited. Univariate and multivariate regression analyses were performed to predict factors relevant for serum CNDP1 concentration. CNDP1 (CTG)(5) homozygous patients with T2D with DN had significantly lower CNDP1 concentrations (30.4 +/- 18.3 vs 51.2 +/- 17.6 mu g/ml, p<0.05) and activity (1.25 +/- 0.5 vs 2.53 +/- 1.1 mu mol/ml/h, p<0.05) than those without nephropathy. This applied for patients with DN on the whole, irrespective of (CTG)(5) homozygosity. In the multivariate regression analyses, lower serum CNDP1 concentrations correlated with impaired renal function and to a lesser extend with the CNDP1 genotype (95% CI of regression coefficients: eGFR: 0.10-1.94 (p=0.001); genotype: -0.05 to 5.79 (p=0.055)). Our study demonstrates that serum CNDP1 concentrations associate with CNDP1 genotype and renal function in patients with T2D. Our data warrant further studies using large cohorts to confirm these findings and to delineate the correlation between low serum CNDP1 concentrations and renal function deterioration in patients with T2D.
引用
收藏
页码:611 / 617
页数:7
相关论文
共 26 条
[1]   Different conformational forms of serum carnosinase detected by a newly developed sandwich ELISA for the measurements of carnosinase concentrations [J].
Adelmann, Katja ;
Frey, Dirk ;
Riedl, Eva ;
Koeppel, Hannes ;
Pfister, Frederick ;
Peters, Verena ;
Schmitt, Claus P. ;
Sternik, Paula ;
Hofmann, Stephanie ;
Zentgraf, Hans Walter ;
Navis, Gerjan ;
van den Born, Jacob ;
Bakker, Stephan J. L. ;
Kraemer, Bernhard K. ;
Yard, Benito A. ;
Hauske, Sibylle J. .
AMINO ACIDS, 2012, 43 (01) :143-151
[2]   Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes [J].
Ahluwalia, T. S. ;
Lindholm, E. ;
Groop, L. C. .
DIABETOLOGIA, 2011, 54 (09) :2295-2302
[3]   The CNDP1 (CTG)5 Polymorphism Is Associated with Biopsy-Proven Diabetic Nephropathy, Time on Hemodialysis, and Diabetes Duration [J].
Albrecht, Thomas ;
Zhang, Shiqi ;
Braun, Jana D. ;
Xia, Li ;
Rodriquez, Angelica ;
Qiu, Jiedong ;
Peters, Verena ;
Schmitt, Claus P. ;
van den Born, Jacob ;
Bakker, Stephan J. L. ;
Lammert, Alexander ;
Koeppel, Hannes ;
Schnuelle, Peter ;
Kraemer, Bernhard K. ;
Yard, Benito A. ;
Hauske, Sibylle J. .
JOURNAL OF DIABETES RESEARCH, 2017, 2017
[4]   Circulating Carnosine Dipeptidase 1 Associates with Weight Loss and Poor Prognosis in Gastrointestinal Cancer [J].
Arner, Peter ;
Henjes, Frauke ;
Schwenk, Jochen M. ;
Darmanis, Spyros ;
Dahlman, Ingrid ;
Iresjo, Britt-Marie ;
Naredi, Peter ;
Agustsson, Thorhallur ;
Lundholm, Kent ;
Nilsson, Peter ;
Ryden, Mikael .
PLOS ONE, 2015, 10 (04)
[5]   Association of variants in the carnosine peptidase 1 gene (CNDP1) with diabetic nephropathy in American Indians [J].
Chakkera, Harini A. ;
Hanson, Robert L. ;
Kobes, Sayuko ;
Millis, Meredith P. ;
Nelson, Robert G. ;
Knowler, William C. ;
DiStefano, Johanna K. .
MOLECULAR GENETICS AND METABOLISM, 2011, 103 (02) :185-190
[6]  
Chandy A, 2008, SAUDI J KIDNEY DIS T, V19, P924
[7]   Causes and Prevention of Protein-Energy Wasting in Chronic Kidney Failure [J].
Dukkipati, Ramnath ;
Kopple, Joel D. .
SEMINARS IN NEPHROLOGY, 2009, 29 (01) :39-49
[8]   Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans [J].
Everaert, Inge ;
Taes, Youri ;
De Heer, Emile ;
Baelde, Hans ;
Zutinic, Ana ;
Yard, Benito ;
Sauerhoefer, Sibylle ;
Vanhee, Lander ;
Delanghe, Joris ;
Aldini, Giancarlo ;
Derave, Wim .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2012, 302 (12) :F1537-F1544
[9]   Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans [J].
Everaert, Inge ;
Mooyaart, Antien ;
Baguet, Audrey ;
Zutinic, Ana ;
Baelde, Hans ;
Achten, Eric ;
Taes, Youri ;
De Heer, Emile ;
Derave, Wim .
AMINO ACIDS, 2011, 40 (04) :1221-1229
[10]   A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans [J].
Freedman, Barry I. ;
Hicks, Pamela J. ;
Sale, Michele M. ;
Pierson, Eric D. ;
Langefeld, Carl D. ;
Rich, Stephen S. ;
Xu, Jianzhao ;
McDonough, Caitrin ;
Janssen, Bart ;
Yard, Benito A. ;
van der Woude, Fokko J. ;
Bowden, Donald W. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2007, 22 (04) :1131-1135