A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients

Georgia Kaidonis; Mark C. Gillies; Sotoodeh Abhary; Ebony Liu; Rohan W. Essex; John H. Chang; Bishwanath Pal; Sobha Sivaprasad; Maria Pefkianaki; Mark Daniell; Stewart Lake; Nikolai Petrovsky; Alex W. Hewitt; Alicia Jenkins; Ecosse L. Lamoureux; Jonathan M. Gleadle; Jamie E. Craig; Kathryn P. Burdon

doi:10.1007/s00592-016-0850-4

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients

Georgia Kaidonis^*, Mark C. Gillies, Sotoodeh Abhary, Ebony Liu, Rohan W. Essex, John H. Chang, Bishwanath Pal, Sobha Sivaprasad, Maria Pefkianaki, Mark Daniell, Stewart Lake, Nikolai Petrovsky, Alex W. Hewitt, Alicia Jenkins, Ecosse L. Lamoureux, Jonathan M. Gleadle, Jamie E. Craig, Kathryn P. Burdon

^*Corresponding author for this work

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Abstract

Aims: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Methods: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, Hb_A1c and hypertension. Results: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM. Conclusions: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

Original language	English
Pages (from-to)	643-650
Number of pages	8
Journal	Acta Diabetologica
Volume	53
Issue number	4
DOIs	https://doi.org/10.1007/s00592-016-0850-4
Publication status	Published - 1 Aug 2016

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Kaidonis, G., Gillies, M. C., Abhary, S., Liu, E., Essex, R. W., Chang, J. H., Pal, B., Sivaprasad, S., Pefkianaki, M., Daniell, M., Lake, S., Petrovsky, N., Hewitt, A. W., Jenkins, A., Lamoureux, E. L., Gleadle, J. M., Craig, J. E., & Burdon, K. P. (2016). A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients. Acta Diabetologica, 53(4), 643-650. https://doi.org/10.1007/s00592-016-0850-4

@article{267820da7e5e4da880b8221b53925be6,

title = "A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients",

abstract = "Aims: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Methods: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. Results: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM. Conclusions: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.",

keywords = "Diabetic macular oedema, Diabetic nephropathy, Diabetic retinopathy, Genetics, microRNA, microRNA-146a",

author = "Georgia Kaidonis and Gillies, {Mark C.} and Sotoodeh Abhary and Ebony Liu and Essex, {Rohan W.} and Chang, {John H.} and Bishwanath Pal and Sobha Sivaprasad and Maria Pefkianaki and Mark Daniell and Stewart Lake and Nikolai Petrovsky and Hewitt, {Alex W.} and Alicia Jenkins and Lamoureux, {Ecosse L.} and Gleadle, {Jonathan M.} and Craig, {Jamie E.} and Burdon, {Kathryn P.}",

note = "Publisher Copyright: {\textcopyright} 2016, Springer-Verlag Italia.",

year = "2016",

month = aug,

day = "1",

doi = "10.1007/s00592-016-0850-4",

language = "English",

volume = "53",

pages = "643--650",

journal = "Acta Diabetologica",

issn = "0940-5429",

publisher = "Springer-Verlag Italia s.r.l.",

number = "4",

}

Kaidonis, G, Gillies, MC, Abhary, S, Liu, E, Essex, RW, Chang, JH, Pal, B, Sivaprasad, S, Pefkianaki, M, Daniell, M, Lake, S, Petrovsky, N, Hewitt, AW, Jenkins, A, Lamoureux, EL, Gleadle, JM, Craig, JE & Burdon, KP 2016, 'A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients', Acta Diabetologica, vol. 53, no. 4, pp. 643-650. https://doi.org/10.1007/s00592-016-0850-4

TY - JOUR

T1 - A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients

AU - Kaidonis, Georgia

AU - Gillies, Mark C.

AU - Abhary, Sotoodeh

AU - Liu, Ebony

AU - Essex, Rohan W.

AU - Chang, John H.

AU - Pal, Bishwanath

AU - Sivaprasad, Sobha

AU - Pefkianaki, Maria

AU - Daniell, Mark

AU - Lake, Stewart

AU - Petrovsky, Nikolai

AU - Hewitt, Alex W.

AU - Jenkins, Alicia

AU - Lamoureux, Ecosse L.

AU - Gleadle, Jonathan M.

AU - Craig, Jamie E.

AU - Burdon, Kathryn P.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Aims: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Methods: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. Results: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM. Conclusions: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

AB - Aims: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Methods: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. Results: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM. Conclusions: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

KW - Diabetic macular oedema

KW - Diabetic nephropathy

KW - Diabetic retinopathy

KW - Genetics

KW - microRNA

KW - microRNA-146a

UR - http://www.scopus.com/inward/record.url?scp=84961246814&partnerID=8YFLogxK

U2 - 10.1007/s00592-016-0850-4

DO - 10.1007/s00592-016-0850-4

M3 - Article

SN - 0940-5429

VL - 53

SP - 643

EP - 650

JO - Acta Diabetologica

JF - Acta Diabetologica

IS - 4

ER -

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients

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