Intercellular adhesion molecule-1 rs5498 in North India: Genetic spark for diabetic retinopathy inflammasome, not yet a clinical beacon

doi:10.4239/wjd.116870

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Diabetes. Aug 15, 2026; 17(8): 116870
Published online Aug 15, 2026. doi: 10.4239/wjd.116870

Intercellular adhesion molecule-1 rs5498 in North India: Genetic spark for diabetic retinopathy inflammasome, not yet a clinical beacon

Yi Luo, Shun-Ping Zhou, Rong Guo

Yi Luo, Shun-Ping Zhou, Rong Guo, Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China

Co-first authors: Yi Luo and Shun-Ping Zhou.

Author contributions: Luo Y and Zhou SP contributed equally to this manuscript and are co-first authors. Luo Y, Guo R and Zhou SP contributed to designing the study; Guo R contributed to preparing the manuscript; Zhou SP and Guo R contributed to revising the draft. All authors have read and approved the final manuscript.

AI contribution statement: DeepL and Grammarly were used for preliminary language translation and grammar checking during the early drafting stage. Additionally, a professional language polishing company utilized AI-assisted editing tools to refine English expression in the revised version. The entirety of the Main Text—including the Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion—was conceived, structured, and written by the authors. No portion of the core scientific content was generated by AI. AI tools were used solely for language polishing and did not contribute to the scientific ideas, experimental design, data analysis, or interpretation presented in the manuscript. AI tools (DeepL, Grammarly) and a professional polishing service were used for English language polishing and translation assistance. However, all data analysis was performed independently by the authors using standard statistical software (e.g., SPSS, R, GraphPad Prism), without AI involvement. The study design, experimental protocol, data collection, statistical analysis, and interpretation of results were conducted entirely by the authors. AI tools played no role in the scientific conception or analytical reasoning of this work. All figures, diagrams, graphs, and tables in the manuscript were created by the authors using conventional scientific plotting and statistical software. No images were generated, modified, or enhanced by AI.

Supported by the Yangpu District Health Commission, No. YPM202415.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Corresponding author: Rong Guo, MD, PhD, Associate Professor, Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, No. 450 Tengyue Road, Shanghai 200090, China. 09_doctorguo@tongji.edu.cn

Received: November 24, 2025
Revised: January 24, 2026
Accepted: March 5, 2026
Published online: August 15, 2026
Processing time: 255 Days and 13.8 Hours

Abstract

In a case-control study involving 614 individuals with type 2 diabetes from northern India published in the World Journal of Diabetes, Kaur et al first reported a 1.6-fold increase in the diabetic retinopathy (DR) among carriers of the intercellular adhesion molecule-1 rs5498 GG genotype, whereas rs1799969 demonstrated no significant association. However, the relatively low odds ratio of 1.6 (95% confidence interval: 1.01-2.53) and population-attributable risk of only approximately 11% limits the clinical utility of genotyping rs5498 as a stand-alone marker. Readers should guard against interpreting this modest effect as justification for immediate clinical adoption. A meta-analysis of nine studies (1844 DR cases, 1595 controls) revealed no overall or Asian-specific association with rs5498, although a modest effect was observed in the Caucasian subgroup. While this study addresses a key data gap in the North-Indian population, employs rigorous phenotyping with validated genotyping, and provides new insights into DR susceptibility, the cross-sectional design, absence of functional data, small effect size, and interethnic heterogeneity preclude immediate clinical translation. Future large-scale longitudinal cohort studies, gene-environment interaction analyses, and multi-omic integration are required to establish the causal relevance of intercellular adhesion molecule-1 variations and to define its potential as a therapeutic target for precise DR prevention.

Keywords: Intercellular adhesion molecule-1 rs5498; Diabetic retinopathy; Genetic association; North-Indian population; Genetic spark

Core Tip: For the first time, the intercellular adhesion molecule-1 rs5498 GG genotype has been linked to an increased risk of diabetic retinopathy in Northern Indians, highlighting the inflammatory genetic architecture of this sight-threatening complication. However, the modest effect size, uncorrected statistical significance, absence of allele-specific expression data, and pronounced inter-ethnic heterogeneity observed in meta-analysis mandate large-scale prospective cohorts, functional validation through Clustered Regularly Interspaced Short Palindromic Repeats-based cellular assays, and multi-omic integration before this variant can be considered for clinical risk stratification or precision prevention strategies.