title: Allelic variation in the CNDP1 gene and its lack of association with longevity and coronary heart disease.
abstract: Carnosine, a cytoprotective dipeptide found at very high concentrations in skeletal muscle, heart and brain, is cleaved in blood by serum carnosinase which is encoded by the CNDP1 gene. We recently found that homozygosity of a 5-leucine variant in the leader peptide of this enzyme protects diabetes mellitus patients against nephropathy. Hypothesising that the same allele could also be associated with longevity or a reduced incidence of cardiovascular problems, we examined the frequency of CNDP1 alleles in German centenarians, patients with premature coronary heart disease, and matched controls. A total of 1382 individuals was investigated. The 5-leucine allele was the most common allele in all groups investigated. There was no difference in allele or genotype frequency between centenarians and their control group, or between cardiovascular patients and their control group. The recently identified functional carnosinase variant therefore does neither contribute to longevity nor protect against coronary heart disease in our probands. In addition to the known trinucleotide repeat alleles in the CNDP1 gene, we detected a rare 8-leucine allele, a rare duplication, p.L13_V15dup, and a more common frameshift deletion, L17fsX20. Homozygosity for L17fsX20, estimated to have a prevalence of approximately 1:20,000, would be expected to cause carnosinaemia, an autosomal recessive trait with uncertain clinical relevance.
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, Germany. johannes.zschocke@med.uni-heidelberg.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
authors.forename: Kate
authors.initials: K
authors.lastname: Wicks
authors.forename: Verena
authors.initials: V
authors.lastname: Peters
authors.forename: Nour Eddine
authors.initials: NE
authors.lastname: El Mokhtari
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Fokko
authors.initials: F
authors.lastname: van der Woude
authors.forename: Bart
authors.initials: B
authors.lastname: Janssen
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003327:Coronary Disease / Q000235:genetics*; D004150:Dipeptidases / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D004150:Dipeptidases; C019673:aminoacyl-histidine dipeptidase