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


Autoria(s): Fagerholm, E; Ahlqvist, E; Forsblom, C; Sandholm, N; Syreeni, A; Parkkonen, M; McKnight, A J; Tarnow, L; Maxwell, A P; Parving, H-H; Groop, L; Groop, P-H; on behalf of the FinnDiane Study Group
Data(s)

01/09/2012

Resumo

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: A SNP predisposing to type 2 diabetes mellitus, rs10811661 near CDKN2A/B, is associated with diabetic nephropathy in patients with type 1 diabetes mellitus.

Identificador

http://pure.qub.ac.uk/portal/en/publications/snp-in-the-genomewide-association-study-hotspot-on-chromosome-9p21-confers-susceptibility-to-diabetic-nephropathy-in-type-1-diabetes(1c8f0b70-7b38-486f-a237-4ed881817ba4).html

http://dx.doi.org/10.1007/s00125-012-2587-0

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Fagerholm , E , Ahlqvist , E , Forsblom , C , Sandholm , N , Syreeni , A , Parkkonen , M , McKnight , A J , Tarnow , L , Maxwell , A P , Parving , H-H , Groop , L , Groop , P-H & on behalf of the FinnDiane Study Group 2012 , ' SNP in the genome-wide association study hotspot on chromosome 9p21 confers susceptibility to diabetic nephropathy in type 1 diabetes ' Diabetologia , vol 55 , no. 9 , pp. 2386-2393 . DOI: 10.1007/s00125-012-2587-0

Palavras-Chave #/dk/atira/pure/subjectarea/asjc/2700/2724 #Internal Medicine #/dk/atira/pure/subjectarea/asjc/2700/2712 #Endocrinology, Diabetes and Metabolism
Tipo

article