Association of IGF1 and VEGFA polymorphisms with diabetic retinopathy in Pakistani population

Autor: Nadia K Waheed, Andrew D. Paterson, Raheel Qamar, Muhammad Ajmal, Delnaz Roshandel, Maleeha Azam, Ali Raza, Netasha Khan
Rok vydání: 2019
Předmět:
Oncology
Adult
Male
Vascular Endothelial Growth Factor A
endocrine system
medicine.medical_specialty
endocrine system diseases
Genotype
Endocrinology
Diabetes and Metabolism
030209 endocrinology & metabolism
Genome-wide association study
Single-nucleotide polymorphism
Type 2 diabetes
030204 cardiovascular system & hematology
Polymorphism
Single Nucleotide
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Endocrinology
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Genetic predisposition
Humans
Genetic Predisposition to Disease
Pakistan
Insulin-Like Growth Factor I
Alleles
Diabetic Retinopathy
business.industry
General Medicine
Diabetic retinopathy
Middle Aged
medicine.disease
Minor allele frequency
Phenotype
Diabetes Mellitus
Type 2
Female
business
Retinopathy
Zdroj: Acta diabetologica. 57(2)
ISSN: 1432-5233
Popis: The incidence of microvascular complications, including diabetic retinopathy (DR), increases with duration of type 2 diabetes (T2D). Meta-GWAS have reported numerous single-nucleotide polymorphisms (SNPs) associated with T2D; however, no loci, achieving genome-wide significance has been reported for DR. Vascular endothelial growth factor A (VEGFA) and insulin-like growth factor 1 (IGF1) are considered as potential genetic candidates involved in T2D and DR progression. Moreover, the association of serum levels of these proteins with diabetes-related traits is controversial. Therefore, the current study was designed to evaluate the possible genetic predisposition and role of these circulating growth factors in serum in the pathophysiology of T2D and DR. A cohort of 1126 individuals with T2D was collected including those without retinopathy (DNR = 573), non-progressive diabetic retinopathy (NPDR = 301) and progressive diabetic retinopathy (PDR = 252), and 348 healthy controls. Genomic DNA was isolated, and six SNPs: rs833061, rs13207351, rs1570360, rs2010963, rs5742632 and rs6214, were genotyped and results statistically analyzed. ELISA was performed on a subset of the samples to measure serum levels of IGF1 and VEGFA. The minor allele of rs6214 was associated with T2D [OR = 1.67 (95% CI 1.39–2.01, p = 4.9E−8)], rs13207351 was associated with NPDR [OR = 1.97 (95% CI 1.28–3.03, p = 9.0E−3)]when compared with DNR, and rs5742632 showed positive association with PDR [OR = 1.66 (95% CI 1.33–2.05, p = 1.0E−4)] compared to DNR. Lowered IGF1 serum levels were found to be associated with T2D, NPDR and PDR. IGF1 was found to increase the T2DM susceptibility as well as advanced DR, i.e., PDR, while VEGFA was found to be associated with early DR stage, i.e., NPDR.
Databáze: OpenAIRE
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