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Diabetologia. 2015 Mar;58(3):543-8. doi: 10.1007/s00125-014-3459-6. Epub 2014 Dec 6.

SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes.

Author information

1
Sorbonne Université, UPMC Université Paris 06, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.

Abstract

AIMS/HYPOTHESIS:

The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy.

METHODS:

We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15 years and no evidence of renal disease.

RESULTS:

None of the single nucleotide polymorphisms (SNPs) tested in a discovery cohort composed of 683 cases and 779 controls reached genome-wide statistical significance. The 46 top hits (p < 10(-5)) were then sought for first-stage analysis in the Genetics of Kidneys in Diabetes US (US-GoKinD) study, an independent population of 820 cases and 885 controls. Two SNPs in strong linkage disequilibrium with each other and located in the SORBS1 gene were consistently and significantly (p < 10(-4)) associated with diabetic nephropathy. The minor rs1326934-C allele was less frequent in cases than in controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic nephropathy (OR 0.70; 95% CI 0.60, 0.82). However, this association was not observed in a second stage with two additional diabetic nephropathy cohorts, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK and Republic of Ireland (UK-ROI; p = 0.15) and the Finnish Diabetic Nephropathy (FinnDiane; p = 0.44) studies, totalling 2,142 cases and 2,494 controls. Altogether, the random-effect meta-analysed rs1326934-C allele OR for diabetic nephropathy was 0.83 (95% CI 0.72, 0.96; p = 0.009).

CONCLUSIONS/INTERPRETATION:

These data suggest that SORBS1 might be a gene involved in diabetic nephropathy.

PMID:
25476525
PMCID:
PMC5438751
DOI:
10.1007/s00125-014-3459-6
[Indexed for MEDLINE]
Free PMC Article

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