Kaur N, Goyal S, Singh IR, Vanita V. Association of ICAM-1 Gene Polymorphisms with Diabetic Retinopathy in T2DM Patients from Northern India: Case-control and meta-analysis. World J Diabetes 2025; 16(12): 110770 [PMID: 41480607 DOI: 10.4239/wjd.v16.i12.110770]
Corresponding Author of This Article
Vanita Vanita, PhD, Professor, Department of Human Genetics, Guru Nanak Dev University, GT Road, Amritsar 143005, Punjab, India. vanita.humangenetics@gmail.com
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Genetics & Heredity
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Case Control Study
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Dec 15, 2025 (publication date) through Mar 22, 2026
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World Journal of Diabetes
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Kaur N, Goyal S, Singh IR, Vanita V. Association of ICAM-1 Gene Polymorphisms with Diabetic Retinopathy in T2DM Patients from Northern India: Case-control and meta-analysis. World J Diabetes 2025; 16(12): 110770 [PMID: 41480607 DOI: 10.4239/wjd.v16.i12.110770]
World J Diabetes. Dec 15, 2025; 16(12): 110770 Published online Dec 15, 2025. doi: 10.4239/wjd.v16.i12.110770
Association of ICAM-1 Gene Polymorphisms with Diabetic Retinopathy in T2DM Patients from Northern India: Case-control and meta-analysis
Navdeep Kaur, Shiwali Goyal, Indu R Singh, Vanita Vanita
Navdeep Kaur, Shiwali Goyal, Vanita Vanita, Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
Indu R Singh, Department of Ophthalmology, Dr. Daljit Singh Eye Hospital, Amritsar 143005, Punjab, India
Co-first authors: Navdeep Kaur and Shiwali Goyal.
Author contributions: Kaur N contributed to the experimental studies and statistical analysis; Kaur N and Goyal S contributed to data analysis and contributed equally to this manuscript to be designated as co-first authors; Singh IR contributed to the clinical studies; Vanita V contributed to the concept and design and definition of intellectual content; Kaur N, Goyal S, and Vanita V contributed to the literature search; Kaur N and Vanita V contributed to the data acquisition; Goyal S and Vanita V contributed to manuscript preparation and editing; All the authors contributed to the manuscript review and read and approved the final version of the manuscript.
Supported by the Department of Biotechnology, Government of India, No. BT/IN/German/13/VK/2010; and the Department of Science and Technology, under the SERC FAST Track scheme for young scientists, No. SR/FT/LS-025/2008.
Institutional review board statement: The current study was approved by the Guru Nanak Dev University’s Ethics Committee (Date: 29 July 2013; No. 1447A/HG) which is in compliance with the 1975 Helsinki Declaration (2013 revision).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: All data generated or analyzed during this study are included in this article.
Corresponding author: Vanita Vanita, PhD, Professor, Department of Human Genetics, Guru Nanak Dev University, GT Road, Amritsar 143005, Punjab, India. vanita.humangenetics@gmail.com
Received: June 16, 2025 Revised: August 17, 2025 Accepted: November 10, 2025 Published online: December 15, 2025 Processing time: 184 Days and 6.8 Hours
Abstract
BACKGROUND
Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults, with prevalence varying by population and reaching ~ 34% in northern India. DR arises from chronic hyperglycemia–driven oxidative stress, inflammation, and microvascular dysfunction. Intercellular adhesion molecule-1 (ICAM-1) is central to leukocyte adhesion and retinal vascular injury; circulating ICAM-1 is elevated in patients and experimental models. Genetic variants in ICAM-1, notably c.1405A>G (rs5498) and c.721G>A (rs1799969), have been examined as risk markers for microvascular complications. Yet associations with DR are inconsistent across ethnicities, and robust data from northern India are limited, underscoring the need for population-specific studies.
AIM
To determine the association of ICAM-1 gene polymorphisms with DR in patients with type 2 diabetes mellitus (T2DM) from northern India.
METHODS
The present study included 614 participants: 302 patients with T2DM and DR and 312 patients with T2DM but without DR. The ICAM-1 polymorphism c.1405A>G (rs5498) was analyzed using PCR-restriction fragment length polymorphism, and analysis of c.721G>A (rs1799969) was done using the amplification-refractory mutation system. Further, approximately 10% of samples were validated for both polymorphisms for the observed genotypes by Sanger sequencing. A meta-analysis incorporating nine studies (1844 DR cases and 1595 controls) was also performed to assess the association of ICAM-1 rs5498 with DR risk.
RESULTS
The allele frequency and genotype distribution of ICAM-1 c.1405A>G polymorphism in the DR and control groups were not significant (P = 0.070 and P = 0.120, respectively). The GG genotype revealed a 1.6-fold increased risk of developing retinopathy (odds ratio = 1.61, 95% confidence interval: 1.01-2.58, P = 0.044). However, the AG genotype did not show any significant association (P = 0.643) between DR cases and controls. With c.721G>A in ICAM-1 the onset and progression of retinopathy was not found to be significantly correlated. The meta-analysis revealed no significant association between rs5498 and DR risk in the overall population or in Asians, but a significant association was observed in Caucasians under the allelic and recessive models.
CONCLUSION
The ICAM-1 rs5498 GG genotype increased retinopathy risk 1.61-fold in northern Indians. Meta-analysis of nine studies found no Asian association; a Caucasian signal warrants caution given limited subgroups and heterogeneity.
Core Tip: This study explored the association of intercellular adhesion molecule-1 gene polymorphisms (rs5498 and rs1799969) with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus from northern India. A significant association was found between the rs5498 GG genotype and increased DR risk. A meta-analysis of nine studies revealed no consistent association overall or in Asians but a significant association in Caucasians. This was the first report from northern India on intercellular adhesion molecule-1 polymorphisms and DR, highlighting the importance of population-specific genetic risk assessment.
