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Diabetologia

Erschienen in:

01.06.2008 | Article

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)

verfasst von: J. K. Hertel, S. Johansson, H. Ræder, K. Midthjell, V. Lyssenko, L. Groop, A. Molven, P. R. Njølstad

Erschienen in: Diabetologia | Ausgabe 6/2008

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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 = 3.9 × 10⁻⁴). 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 = 8.4 × 10⁻⁴).

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.

Nur mit Berechtigung zugänglich

Permutt MA, Wasson J, Cox N (2005) Genetic epidemiology of diabetes. J Clin Invest 115:1431–1439PubMedCrossRef

Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885PubMedCrossRef

Saxena R, Voight BF, Lyssenko V et al (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336PubMedCrossRef

Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341PubMedCrossRef

Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345PubMedCrossRef

Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:770–775PubMedCrossRef

Holmen J, Midthjell K, Krüger Ø et al (2003) The Nord-Trøndelag Health Study 1995–97 (HUNT2): objectives, contents, methods and participation. Norw J Epidemiol 13:19–32

Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894PubMedCrossRef

Dina C, Meyre D, Gallina S et al (2007) Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 39:724–726PubMedCrossRef

10.

Scuteri A, Sanna S, Chen WM et al (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:e115PubMedCrossRef

11.

Midthjell K, Krüger O, Holmen J et al (1999) Rapid changes in the prevalence of obesity and known diabetes in an adult Norwegian population. The Nord-Trøndelag Health Surveys: 1984–1986 and 1995–1997. Diabetes Care 22:1813–1820PubMedCrossRef

12.

Midthjell K, Holmen J, Bjørndal A et al (1992) Is questionnaire information valid in the study of a chronic disease such as diabetes? The Nord-Trøndelag diabetes study. J Epidemiol Community Health 46:537–542PubMedCrossRef

13.

Johansson S, Raeder H, Eide SA et al (2007) Studies in 3,523 Norwegians and meta-analysis in 11,571 subjects indicate that variants in the hepatocyte nuclear factor 4 alpha (HNF4A) P2 region are associated with type 2 diabetes in Scandinavians. Diabetes 56:3112–3117PubMedCrossRef

14.

Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRef

15.

Purcell S, Cherny SS, Sham PC (2003) Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150PubMedCrossRef

16.

Grant SF, Thorleifsson G, Reynisdottir I et al (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323PubMedCrossRef

17.

Florez JC, Burtt N, de Bakker PI et al (2004) Haplotype structure and genotype–phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes 53:1360–1368PubMedCrossRef

18.

Samani NJ, Erdmann J, Hall AS et al (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453PubMedCrossRef

19.

Helgadottir A, Thorleifsson G, Manolescu A et al (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316:1491–1493PubMedCrossRef

20.

McPherson R, Pertsemlidis A, Kavaslar N et al (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488–1491PubMedCrossRef

21.

De Silva NM, Steele A, Shields B et al (2007) The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies. Diabet Med 24:1067–1072PubMedCrossRef

22.

Lyssenko V, Lupi R, Marchetti P et al (2007) Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117:2155–2163PubMedCrossRef

23.

Grarup N, Rose CS, Andersson EA et al (2007) Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 56:3105–3111PubMedCrossRef

Titel: 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)
verfasst von: J. K. Hertel
S. Johansson
H. Ræder
K. Midthjell
V. Lyssenko
L. Groop
A. Molven
P. R. Njølstad
Publikationsdatum: 01.06.2008
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 6/2008
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-008-0982-3

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