Genetic Polymorphism in Patients with Diabetic Nephropathy and Retinopathy: A Cross-sectional Study
Introduction: The chronic persistence of diabetes leads to microvascular complications, such as Diabetic Nephropathy (DN) and Diabetic Retinopathy (DR). Both of these are progressive disorders involving pathological changes in capillaries. A few biochemical pathways have been suggested to link...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
JCDR Research and Publications Private Limited
2023-08-01
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| Series: | Journal of Clinical and Diagnostic Research |
| Subjects: | |
| Online Access: | https://www.jcdr.net/articles/PDF/18378/64099_CE[Ra1]_F(IS)_QC(SHK_OM)_PF1(RI_OM_KM)_PFA(RI_KM)_PN(KM).pdf |
| Summary: | Introduction: The chronic persistence of diabetes leads to
microvascular complications, such as Diabetic Nephropathy (DN)
and Diabetic Retinopathy (DR). Both of these are progressive
disorders involving pathological changes in capillaries. A
few biochemical pathways have been suggested to link
hyperglycaemia and microvascular complications. The probability
of developing and progressing DN and DR is associated with
the duration of diabetes. These complex disorders are strongly
influenced by both genetics and environmental factors. Several
candidate genes have been reported to be associated with DN
and DR in different populations.
Aim: To determine the co-existence of DN and DR in relation to
gene polymorphisms of Angiotensin-Converting Enzyme (ACE),
Angiotensinogen (AGT), Receptor for Advanced Glycation
End-products (RAGE), Aldose reductase (ALR2), and Vascular
Endothelial Growth Factor (VEGF).
Materials and Methods: The present DN and DR cross-sectional
study was conducted at the Department of Endocrinology,
University College of Medical Sciences, University of Delhi and
GTB, New Delhi, India, and the Discipline of Biochemistry, Indira
Gandhi National Open University, New Delhi, India. The study
was conducted from October 2019 to August 2022. All the
participants under uniform diabetes management were divided
into two groups (100 in each group): Group 1 included Type-II
diabetic patients with DN and DR, and Group 2 comprised Type-II
diabetic patients with DN only. Polymorphisms in all genes were
determined using Polymerase Chain Reaction (PCR), followed
by digestion with restriction enzymes and visualisation through
an ultraviolet transilluminator. The analysis of biochemical
parameters and association of gene polymorphisms was
performed using Statistical Package for Social Sciences (SPSS)
version 26.0 software.
Results: There were 57 males and 43 females in the DN+DR
group, and 51 males and 49 females in the DN-DR group. The
mean age of study subjects in the DN+DR group was 52.60±9.08
years, compared to the DN-DR group (47.33±10.68 years).
The DN+DR group had a significantly higher mean duration of
diabetes (11.78±6.86 vs. 5.13±4.78, p≤0.001) and a significantly
lower mean waist circumference (91.30±13.99 vs. 95.11±9.95
cm, p≤0.02). The DN+DR group also had significantly higher
urea (34.34±16.32 vs. 26.43±12.34 cm, p≤0.001), creatinine
(1.34±0.90 vs. 0.89±0.25 cm, p≤0.03) and significantly lower
estimated Glomerular Filtration Rate (eGFR) levels compared to
the DN-DR group. The distribution of genotypes of ALR2 (p≤0.04)
and VEGF genes (p≤0.001) showed a significant difference
between both DN+DR and DN-DR groups. The frequency of the
D allele of the VEGF gene (p≤0.02) (OR=1.94, 95% Confidence
Interval (CI)=1.10-3.40) was higher in the DN+DR group. The
DN+DR group also had a significantly lower frequency of the
CT+TT dominant model of the ALR2 gene (p≤0.04) as well as
an increased frequency of the ID+DD dominant model of the
VEGF gene (p≤0.002). No significant differences were found in
genotypic as well as allelic frequencies of ACE, AGT, and RAGE
gene polymorphisms between the two groups.
Conclusion: The D allele of the VEGF (I/D) gene polymorphism
is significantly associated with DR in patients with DN. It can be
concluded that the VEGF gene plays an important role in the
development of retinopathy in DN patients. |
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| ISSN: | 2249-782X 0973-709X |