Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes

S. Alkayyali, M. Lajer, H. Deshmukh, E. Ahlqvist, H. Colhoun, B. Isomaa, P. Rossing, L. Groop, V. Lyssenko

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Aims/hypothesis

Type 2 diabetes is a chronic metabolic disorder associated with devastating
microvascular complications. Genome-wide association studies have
identified more than 60 genetic variants associated with type 2 diabetes
and/or glucose and insulin traits, but their role in the progression of
diabetes is not established. The aim of this study was to explore
whether these variants were also associated with the development of
nephropathy in patients with type 2 diabetes.

Methods

We studied 28 genetic variants in 2,229 patients with type 2 diabetes from
the local Malmö Scania Diabetes Registry (SDR) published during
2007?2010. Diabetic nephropathy (DN) was defined as micro- or
macroalbuminuria and/or end-stage renal disease. Estimated glomerular
filtration rate (eGFR) was assessed using the MDRD-4 formula.
Replication genotyping of rs1531343 was performed in diabetic (Steno
type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts.

Results

In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, ß ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, ß ± SEM, -0.008 ± 0.003 ml/min (log e ), p = 0.006).

Conclusions/interpretation

These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing  nephropathy in patients with type 2 diabetes and lower eGFR in both  diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney
complications.

Original languageEnglish
Pages (from-to)323-329
Number of pages7
JournalDiabetologia
Volume56
Issue number2
Publication statusPublished - 2013

Keywords / Materials (for Non-textual outputs)

  • Diabetes complications RISK Type 2 diabetes GLOMERULAR-FILTRATION-RATE HMGA2 COMPLICATIONS FASTING GLUCOSE MELLITUS Nephropathy SNP MICROALBUMINURIA PROTEINS ASSOCIATION KIDNEY-FUNCTION LOCI

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