MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus

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

doi:10.1167/iovs.18-25570

MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus

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

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

36 Downloads (Pure)

Abstract

Purpose: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.

Original language	English
Pages (from-to)	3937-3942
Number of pages	6
Journal	Investigative Ophthalmology & Visual Science
Volume	60
Issue number	12
DOIs	https://doi.org/10.1167/iovs.18-25570
Publication status	Published - 1 Sept 2019

Bibliographical note

Copyright 2019 The Authors
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords

diabetes
retinopathy
genetic variants
Diabetic retinopathy
MicroRNA
Type 1 diabetes
Caucasian
Genetic variants

UN SDGs

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

Access to Document

10.1167/iovs.18-25570Licence: CC BY-NC-ND

i1552-5783-60-12-3937Licence: CC BY-NC-ND

Cite this

Liu, E., Kaidonis, G., McComish, B. J., Gillies, M. C., Abhary, S., Essex, R. W., Chang, J. H., Pal, B., Daniell, M., Lake, S., Petrovsky, N., Hewitt, A. W., Jenkins, A., Lamoureux, E. L., Gleadle, J. M., Craig, J. E., & Burdon, K. P. (2019). MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus. Investigative Ophthalmology & Visual Science, 60(12), 3937-3942. https://doi.org/10.1167/iovs.18-25570

@article{915a79d7ee844d90817441ec2e9b6496,

title = "MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus",

abstract = "Purpose: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.",

keywords = "diabetes, retinopathy, genetic variants, Diabetic retinopathy, MicroRNA, Type 1 diabetes, Caucasian, Genetic variants",

author = "Ebony Liu and Georgia Kaidonis and McComish, {Bennet J.} and Gillies, {Mark C.} and Sotoodeh Abhary and Essex, {Rohan W.} and Chang, {John H.} and Bishwanath Pal 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.}",

year = "2019",

month = sep,

day = "1",

doi = "10.1167/iovs.18-25570",

language = "English",

volume = "60",

pages = "3937--3942",

journal = "Investigative Ophthalmology & Visual Science",

issn = "1552-5783",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "12",

}

Liu, E, Kaidonis, G, McComish, BJ, Gillies, MC, Abhary, S, Essex, RW, Chang, JH, Pal, B, Daniell, M, Lake, S, Petrovsky, N, Hewitt, AW, Jenkins, A, Lamoureux, EL, Gleadle, JM , Craig, JE & Burdon, KP 2019, 'MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus', Investigative Ophthalmology & Visual Science, vol. 60, no. 12, pp. 3937-3942. https://doi.org/10.1167/iovs.18-25570

TY - JOUR

T1 - MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus

AU - Liu, Ebony

AU - Kaidonis, Georgia

AU - McComish, Bennet J.

AU - Gillies, Mark C.

AU - Abhary, Sotoodeh

AU - Essex, Rohan W.

AU - Chang, John H.

AU - Pal, Bishwanath

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 - 2019/9/1

Y1 - 2019/9/1

N2 - Purpose: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.

AB - Purpose: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.

KW - diabetes

KW - retinopathy

KW - genetic variants

KW - Diabetic retinopathy

KW - MicroRNA

KW - Type 1 diabetes

KW - Caucasian

KW - Genetic variants

UR - http://www.scopus.com/inward/record.url?scp=85072571156&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/NHMRC/595918

U2 - 10.1167/iovs.18-25570

DO - 10.1167/iovs.18-25570

M3 - Article

C2 - 31546259

AN - SCOPUS:85072571156

SN - 1552-5783

VL - 60

SP - 3937

EP - 3942

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 12

ER -

MicroRNA-Related Genetic Variants Are Associated With Diabetic Retinopathy in Type 1 Diabetes Mellitus

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this