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.
N1 - Publisher Copyright:
© 2019 The Authors.
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 genomewide 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. χ 2 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 sightthreatening 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 genomewide 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. χ 2 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 sightthreatening DR.
KW - Caucasian
KW - Diabetic retinopathy
KW - Genetic variants
KW - MicroRNA
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85072571156&partnerID=8YFLogxK
U2 - 10.1167/iovs.18-25570
DO - 10.1167/iovs.18-25570
M3 - Article
SN - 0146-0404
VL - 60
SP - 3937
EP - 3942
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 12
ER -