Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)

Hertel, J K; Johansson, S; Raeder, H; Midthjell, K; Lyssenko, Valeriya; Groop, Leif; Molven, A; Njolstad, P R

Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)

Mark

Hertel, J K ; Johansson, S ; Raeder, H ; Midthjell, K ; Lyssenko, Valeriya ^LU ; Groop, Leif ^LU ; Molven, A and Njolstad, P R (2008) In Diabetologia 51(6). p.971-977

Abstract: Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol... (More); Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs. Results We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9x10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4x10(-4)). Conclusions/interpretation Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/1204798

author

Hertel, J K ; Johansson, S ; Raeder, H ; Midthjell, K ; Lyssenko, Valeriya ^LU ; Groop, Leif ^LU ; Molven, A and Njolstad, P R

organization

Translational Muscle Research (research group)

publishing date

2008

type

Contribution to journal

publication status

published

subject

Endocrinology and Diabetes

keywords

susceptibility gene, SNP, polymorphism, single nucleotide, replication, GWA, association study, BMI, type 2 diabetes

in

Diabetologia

volume

51

issue

6

pages

971 - 977

publisher

Springer

external identifiers

wos:000255537000011
scopus:43049149732
pmid:18437351

ISSN

1432-0428

DOI

10.1007/s00125-008-0982-3

language

English

LU publication?

yes

id

0222caf8-4dd2-4fff-ad2a-75ef0989def0 (old id 1204798)

date added to LUP

2016-04-01 11:48:10

date last changed

2024-01-07 21:06:04

@article{0222caf8-4dd2-4fff-ad2a-75ef0989def0,
  abstract     = {{Aims/hypothesis Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study). Methods We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs. Results We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9x10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4x10(-4)). Conclusions/interpretation Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.}},
  author       = {{Hertel, J K and Johansson, S and Raeder, H and Midthjell, K and Lyssenko, Valeriya and Groop, Leif and Molven, A and Njolstad, P R}},
  issn         = {{1432-0428}},
  keywords     = {{susceptibility gene; SNP; polymorphism; single nucleotide; replication; GWA; association study; BMI; type 2 diabetes}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{971--977}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)}},
  url          = {{http://dx.doi.org/10.1007/s00125-008-0982-3}},
  doi          = {{10.1007/s00125-008-0982-3}},
  volume       = {{51}},
  year         = {{2008}},
}

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Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study)