BACKGROUND: Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs. METHODS: We evaluated the role of the CNDP1 5 leucine/5 leucine (5-5) polymorphism (CNDP1 Mannheim) in diabetic end-stage renal disease (ESRD) susceptibility in 858 European Americans: 294 with type 2 DN-associated ESRD (DN-ESRD), 258 with diabetes mellitus (DM) lacking nephropathy and 306 healthy controls. RESULTS: Subjects with DM lacking nephropathy were significantly more likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared with those with DN-ESRD (P=0.02). Healthy controls were also more likely to be homozygous for the 5-5 genotype, compared with those with DN-ESRD (P=0.008). No significant difference in 5-5 genotype frequency was observed between healthy controls and DM cases without nephropathy (P=0.74). CONCLUSION: European Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene are at significantly reduced risk for developing diabetic ESRD. This replicates the CNDP1 gene association with DN that was initially detected in European Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and carnosine pathway appear to play a role in susceptibility to DN.
BACKGROUND: Four linkage analyses have identified a region on chromosome 18q22-23 that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs. METHODS: We evaluated the role of the CNDP1 5 leucine/5 leucine (5-5) polymorphism (CNDP1 Mannheim) in diabetic end-stage renal disease (ESRD) susceptibility in 858 European Americans: 294 with type 2 DN-associated ESRD (DN-ESRD), 258 with diabetes mellitus (DM) lacking nephropathy and 306 healthy controls. RESULTS: Subjects with DM lacking nephropathy were significantly more likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared with those with DN-ESRD (P=0.02). Healthy controls were also more likely to be homozygous for the 5-5 genotype, compared with those with DN-ESRD (P=0.008). No significant difference in 5-5 genotype frequency was observed between healthy controls and DM cases without nephropathy (P=0.74). CONCLUSION: European Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene are at significantly reduced risk for developing diabetic ESRD. This replicates the CNDP1 gene association with DN that was initially detected in European Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and carnosine pathway appear to play a role in susceptibility to DN.
Authors: Sulgi Kim; Hanna E Abboud; Madeleine V Pahl; John Tayek; Susan Snyder; James Tamkin; Harry Alcorn; Eli Ipp; Cynthia C Nast; Robert C Elston; Sudha K Iyengar; Sharon G Adler Journal: Clin J Am Soc Nephrol Date: 2010-03-18 Impact factor: 8.237
Authors: A Alkhalaf; G W D Landman; K J J van Hateren; K H Groenier; A L Mooyaart; E De Heer; R O B Gans; G J Navis; S J L Bakker; N Kleefstra; H J G Bilo Journal: J Nephrol Date: 2014-04-23 Impact factor: 3.902
Authors: Antien L Mooyaart; Ana Zutinic; Stephan J L Bakker; Diana C Grootendorst; Nanne Kleefstra; Irene G M van Valkengoed; Stefan Böhringer; Henk J G Bilo; Friedo W Dekker; Jan Anthonie Bruijn; Gerjan Navis; Bart Janssen; Hans J Baelde; Emile De Heer Journal: Diabetes Date: 2010-03-23 Impact factor: 9.461
Authors: Eva Riedl; Hannes Koeppel; Frederick Pfister; Verena Peters; Sibylle Sauerhoefer; Paula Sternik; Paul Brinkkoetter; Hanswalter Zentgraf; Gerjan Navis; Robert H Henning; Jacob Van Den Born; Stephan J L Bakker; Bart Janssen; Fokko J van der Woude; Benito A Yard Journal: Diabetes Date: 2010-05-11 Impact factor: 9.461