Impact of VEGF Gene Polymorphisms on Progression of Diabetic Retinopathy in an Indian Population
Authors: Jajal Dhara , Kalia Kiran 
Published: November 2023

Vascular endothelial growth factor (VEGF) is a chief chemokine that mediates angiogenesis during tissue growth and organ repair processes. Elevated circulating VEGF levels are inferred to play a pivotal role in type 2 diabetes microvascular complications, particularly diabetic retinopathy (DR). Previous genome‐wide association studies indicated major SNPs in the promoter and UTR regions of VEGF gene that confer risk to the development and progression of DR. Alternatively, not many studies considered intronic SNPs for the same and need to be investigated. The present study was aimed to identify the impact of three intronic SNPs of VEGF gene on the progression of diabetic retinopathy, as well as on its related traits like duration of diabetes and glycated hemoglobin (GHb). We genotyped rs833069, rs2146323, and rs3025021 SNPs by PCR‐RFLP technique in 110 type 2 diabetes patients without retinopathy (DC‐diabetic control) and 148 type 2 diabetes patients with retinopathy (DR) of the India.

We found the association of AA genotype of rs2146323 with the increased DR risk (p = 0.044, OR = 2.57, 95% CI = 1.06 – 6.25). Further, AA genotype and A allele were strongly associated with the severity of DR after Bonferroni correction (p = 0.003, OR = 4.3, 95% CI = 1.63 – 11.32 and p = 0.01, OR = 1.82, 95% CI = 1.16 – 2.87, respectively). We observed the same genotype significantly higher among proliferative diabetic retinopathy patients with diabetes duration less than 10 years, which was not the case in patients with diabetes duration more than 10 years (p = 0.001 vs p = 0.22). The allelic and genotypic frequencies of rs833069 and rs3025021 did not significantly differ between the study groups. Likewise, none of the allele or genotypes was found to be associated with GHb levels.

In conclusion, the current study indicated the recessive model of rs2146323 to potentially influence the rate of DR occurrence by more than two‐fold in the targeted Indian ethnicity. The SNP may be in high linkage disequilibrium in particular ethnicity with other SNPs that has shown functional and genetic association with DR and need to be studied in the current population. Eventually, such studies would help in identifying patients at high risk of DR comparatively early that can be delayed with frequent retinal monitoring programs.

Support or Funding Information

The present study was financially supported by the University Grant Commission (UGC), New Delhi, India under “Major Research Project” Scheme (Sanction Letter No. F.‐42‐637/2013(SR) dated 22/03/2013).

Comparisons of Genotypic and Allelic distribution of VEGF gene polymorphisms among the study groups

Comparisons of Genotype and allele distributions

SNP
DC vs. DR
DC vs. PDR

P value
OR (95% CI)
P value
OR (95% CI)

rs833069 (3596 T>C)
T/T + T/C vs C/C
1.0
1.12 (0.31 – 4.07)
0.705
1.35 (0.29 – 6.22)

T vs C
0.756
1.07 (0.71 – 1.61)
0.127
1.48 (0.91 – 2.42)

rs2146323 (6112C>A)
C/C+C/A vs A/A
0.044
2.57 (1.06 – 6.25)
0.003
4.3 (1.63 – 11.32)

C vs A
0.138
1.32 (0.91 – 1.91)
0.01
1.82 (1.16 – 2.87)

rs3025021 (10180C>T)
C/C+C/T vs T/T
0.176
2.10 (0.79 – 5.56)
0.052
2.94 (0.99 – 8.71)

C vs T
0.769
0.94 (0.64 – 1.37)
0.62
1.15 (0.72 – 1.85)