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

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    15 Citations (Scopus)

    Abstract

    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
    DOIs
    Publication statusPublished - Feb 2013

    Keywords

    • 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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