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Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.

Ahluwalia, Tarun LU ; Lindholm, Eero LU and Groop, Leif LU (2011) In Diabetologia 54. p.2295-2302
Abstract
AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-: histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. METHODS: We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up... (More)
AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-: histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. METHODS: We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry). RESULTS: Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (β = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001). CONCLUSIONS/INTERPRETATION: These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetologia
volume
54
pages
2295 - 2302
publisher
Springer Verlag
external identifiers
  • wos:000293544900015
  • pmid:21573905
  • scopus:80054695458
ISSN
1432-0428
DOI
10.1007/s00125-011-2178-5
language
English
LU publication?
yes
id
cac65ab7-f2b8-42e1-9647-ddfdcbe59e2f (old id 1972559)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21573905?dopt=Abstract
date added to LUP
2011-06-07 19:32:48
date last changed
2017-09-03 03:01:50
@article{cac65ab7-f2b8-42e1-9647-ddfdcbe59e2f,
  abstract     = {AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-: histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. METHODS: We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry). RESULTS: Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (β = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p &lt; 0.0001). CONCLUSIONS/INTERPRETATION: These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.},
  author       = {Ahluwalia, Tarun and Lindholm, Eero and Groop, Leif},
  issn         = {1432-0428},
  language     = {eng},
  pages        = {2295--2302},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.},
  url          = {http://dx.doi.org/10.1007/s00125-011-2178-5},
  volume       = {54},
  year         = {2011},
}