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

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Abstract

Aims

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.

Methods

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.

Results

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.

Conclusions

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.

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Funding

The study has been supported by the Higher Education Commission of Pakistan (Grant Nos. 3738 and 20-4885) and Pakistan Academy of Sciences (Grant No. 5-9/PAAS/1082) given to MA and RQ.

Author information

Authors and Affiliations

  1. Translational Genomics Laboratory, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad, 45600, Pakistan

    Netasha Khan, Muhammad Ajmal, Maleeha Azam & Raheel Qamar

  2. Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada

    Netasha Khan, Andrew D. Paterson & Delnaz Roshandel

  3. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Andrew D. Paterson

  4. Department of Ophthalmology, Rawalpindi Medical University, Rawalpindi, Pakistan

    Ali Raza

  5. Tufts University Medical School, Boston, USA

    Nadia K. Waheed

  6. Pakistan Academy of Sciences, Islamabad, Pakistan

    Raheel Qamar

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  1. Netasha Khan
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Correspondence to Maleeha Azam or Raheel Qamar.

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The study conforms to the Declaration of Helsinki and was approved by the Ethics Review Board of the Department of Biosciences at COMSATS University Islamabad, Pakistan.

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Khan, N., Paterson, A.D., Roshandel, D. et al. Association of IGF1 and VEGFA polymorphisms with diabetic retinopathy in Pakistani population. Acta Diabetol 57, 237–245 (2020). https://doi.org/10.1007/s00592-019-01407-5

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