Mol Biol Rep: Association of candidate gene (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in patients with type 2 diabetes

Background: Diabetic retinopathy (DR) is a complication of diabetes, a chronic condition
associated with high blood sugar.
DR is a progressive retinal disease involving lesions of capillaries resulting in one or more abnormal features that are identified
by trained observers during diagnosis.
The probability of occurrence and development of diabetic retinopathy is related
to the course of diabetes.
Within the first 10 years of being diagnosed with diabetes, all people with type 1 diabetes and more than 60 percent of people with type 2 diabetes are expected to develop some kind of retinopathy
.

Diabetic retinopathy is divided into non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PPDR), and proliferative diabetic retinopathy (PDR).

Notable features of NPDR include microaneurysms, cotton spots, hard exudates, venous beading, and intraretinal microvascular abnormalities
.
This condition either remains stable or persists in developing into PDR, which can be identified
by neovascularization, preretinal hemorrhage, and vitreous hemorrhage.
In patients with diabetic retinopathy, diabetic macular edema (DME) is the most common cause of vision loss and is characterized by thickening or swelling of the macula due to disruption of the retinal blood barrier (BRB) that activates fluid accumulation within and under the macula
.
For screening for diabetic retinopathy, several different diagnostic methods are used, in particular slit lamp biomicroscopy, direct or indirect fundus examination, mydriatic (diffuse) or non-dilated (non-dilated) digital fundus photography
.

In 2010, a rough count of 93 million people worldwide had diabetic retinopathy and 28 million were affected
by vision-threatening diabetic retinopathy (VTDR).
Diabetic retinopathy can become a leading cause
of blindness worldwide.
According to the Wisconsin Diabetic Retinopathy Epidemiological Study (WESDR), about 3.
6 percent of people with type 1 diabetes and 1.
6 percent of people with type 2 diabetes are legally blind
.
Due to the alarming incidence of diabetes, the incidence of diabetic retinopathy is expected to increase to 191 million
by 2030.

Objective: To investigate the relationship
between glycosylated end-product receptor (RAGE, rs2070600) and vascular endothelial growth factor (VEGF, rs833061) and retinopathy in patients with type 2 diabetes mellitus in Khyber-Pakhtunkhwa region.

Methods: A case-control study
was conducted in 550 patients with diabetic retinopathy (DR) complicated with type 2 diabetes mellitus (DR), 180 patients with type 2 diabetes mellitus (T2 DM) and 184 healthy controls (HC).
All samples were extracted by salting out and SNP genotyping
by Tetra-Arm polymerase chain reaction.
Alleles and genotype distributions were tested using chi-square tests and exact Fischer tests
.
The odd ratio and continuous interval values
are calculated using the online software MedCalc odd ratio calculator.

Results: Compared with DM and HC, random blood glucose (P<0.
001), fasting blood glucose (P<0.
001), glycated hemoglobin (P<0.
001), total cholesterol (P<0.
001), low-density lipoprotein (P<0.
001), high-density lipoprotein (P<0.
001), body mass index (P<0.
001), hypertension (P=0.
018) and other indexes were closely related to the occurrence of DR
。 The results showed that vascular endothelial growth factor rs833061 (p<.
001 rs2070600 >

Table 1 Clinical parameters of
pregnant women with diabetic retinopathy and type 2 diabetes mellitus compared with healthy control groups.

Table 2 Relationships between vascular endothelial growth factor, ALR2 and RAGE gene polymorphisms with DR, T2DM and control groups

Table 3 Distribution of gene frequencies and allele frequencies in the diabetic retinopathy group

Conclusion: There is a significant correlation
between vascular endothelial growth factor rs833061 and RAGE rs2070600 and type 2 diabetic retinopathy.
In addition, this is the first time that the relationship between
RAGE and diabetic retinopathy in type 2 diabetic patients in Khyber-Pakhtunkhwa populations has been reported.

Jehanzeb M, Khan NU, Hussain M, et al.
Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic reopathy in type 2 diabetic patients of Khyber Pakhtunkhwa, Pakistan.
Mol Biol Rep 2022 Nov 01