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SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes

Fagerholm, E.; Ahlqvist, Emma LU ; Forsblom, C.; Sandholm, N.; Syreeni, A.; Parkkonen, M.; McKnight, A. J.; Tarnow, L.; Maxwell, A. P. and Parving, H. -H., et al. (2012) In Diabetologia 55(9). p.2386-2393
Abstract
Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three... (More)
Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p = 0.00045, p (36tests) = 0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p = 0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p = 0.0040), but the association did not remain after Bonferroni correction (p (36tests) = 0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus. (Less)
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published
subject
keywords
CDKN2A, Diabetic nephropathy, Genetics, rs10811661, Type 1 diabetes, mellitus, Type 2 diabetes mellitus
in
Diabetologia
volume
55
issue
9
pages
2386 - 2393
publisher
Springer Verlag
external identifiers
  • wos:000307301800014
  • scopus:84866130556
ISSN
1432-0428
DOI
10.1007/s00125-012-2587-0
language
English
LU publication?
yes
id
c0c2b51f-83c1-4945-bbdf-260d4629bf12 (old id 3055685)
date added to LUP
2012-10-05 07:16:41
date last changed
2017-06-25 03:27:02
@article{c0c2b51f-83c1-4945-bbdf-260d4629bf12,
  abstract     = {Parental type 2 diabetes mellitus increases the risk of diabetic nephropathy in offspring with type 1 diabetes mellitus. Several single nucleotide polymorphisms (SNPs) that predispose to type 2 diabetes mellitus have recently been identified. It is, however, not known whether such SNPs also confer susceptibility to diabetic nephropathy in patients with type 1 diabetes mellitus. We genotyped nine SNPs associated with type 2 diabetes mellitus in genome-wide association studies in the Finnish population, and tested for their association with diabetic nephropathy as well as with severe retinopathy and cardiovascular disease in 2,963 patients with type 1 diabetes mellitus. Replication of significant SNPs was sought in 2,980 patients from three other cohorts. In the discovery cohort, rs10811661 near gene CDKN2A/B was associated with diabetic nephropathy. The association remained after robust Bonferroni correction for the total number of tests performed in this study (OR 1.33 [95% CI 1.14, 1.56], p = 0.00045, p (36tests) = 0.016). In the meta-analysis, the combined result for diabetic nephropathy was significant, with a fixed effects p value of 0.011 (OR 1.15 [95% CI 1.02, 1.29]). The association was particularly strong when patients with end-stage renal disease were compared with controls (OR 1.35 [95% CI 1.13, 1.60], p = 0.00038). The same SNP was also associated with severe retinopathy (OR 1.37 [95% CI 1.10, 1.69] p = 0.0040), but the association did not remain after Bonferroni correction (p (36tests) = 0.14). None of the other selected SNPs was associated with nephropathy, severe retinopathy or cardiovascular disease. A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.},
  author       = {Fagerholm, E. and Ahlqvist, Emma and Forsblom, C. and Sandholm, N. and Syreeni, A. and Parkkonen, M. and McKnight, A. J. and Tarnow, L. and Maxwell, A. P. and Parving, H. -H. and Groop, Leif and Groop, P. -H.},
  issn         = {1432-0428},
  keyword      = {CDKN2A,Diabetic nephropathy,Genetics,rs10811661,Type 1 diabetes,mellitus,Type 2 diabetes mellitus},
  language     = {eng},
  number       = {9},
  pages        = {2386--2393},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-012-2587-0},
  volume       = {55},
  year         = {2012},
}