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

doi:10.1007/s00125-012-2760-5

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 journal › Article › peer-review

20 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 language	English
Pages (from-to)	323-329
Number of pages	7
Journal	Diabetologia
Volume	56
Issue number	2
DOIs	https://doi.org/10.1007/s00125-012-2760-5
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00125-012-2760-5

Cite this

@article{1dbc533777bb43d997bdc90b28f4eed4,

title = "Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes",

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 Malm{\"o} 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 (Malm{\"o} 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. ",

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

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

year = "2013",

month = feb,

doi = "10.1007/s00125-012-2760-5",

language = "English",

volume = "56",

pages = "323--329",

journal = "Diabetologia",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "2",

}

TY - JOUR

T1 - Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes

AU - Alkayyali, S.

AU - Lajer, M.

AU - Deshmukh, H.

AU - Ahlqvist, E.

AU - Colhoun, H.

AU - Isomaa, B.

AU - Rossing, P.

AU - Groop, L.

AU - Lyssenko, V.

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - Diabetes complications

KW - RISK

KW - Type 2 diabetes

KW - GLOMERULAR-FILTRATION-RATE

KW - HMGA2

KW - COMPLICATIONS

KW - FASTING GLUCOSE

KW - MELLITUS

KW - Nephropathy

KW - SNP

KW - MICROALBUMINURIA

KW - PROTEINS

KW - ASSOCIATION

KW - KIDNEY-FUNCTION

KW - LOCI

U2 - 10.1007/s00125-012-2760-5

DO - 10.1007/s00125-012-2760-5

M3 - Article

C2 - 23111731

VL - 56

SP - 323

EP - 329

JO - Diabetologia

JF - Diabetologia

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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