Genetic variants and type 2 diabetes in India: a systematic review and meta-analysis of associated polymorphisms in case-control studies

Lokendra Rathod; Sameera Khan; Sweta Mishra; Deepanker Das; Kaustubh Bora; Swasti Shubham; Samradhi Singh; Manoj Kumar; Rajnarayan R Tiwari; Archana Tiwari; Pradyumna Kumar Mishra; Devojit Kumar Sarma

doi:10.1016/j.lansea.2024.100518

Genetic variants and type 2 diabetes in India: a systematic review and meta-analysis of associated polymorphisms in case-control studies

Lancet Reg Health Southeast Asia. 2024 Dec 10:32:100518. doi: 10.1016/j.lansea.2024.100518. eCollection 2025 Jan.

Authors

Affiliations

¹ ICMR - National Institute for Research in Environmental Health, Bhopal, Madhya Pradesh, India.
² School of Bimolecular Engineering & Biotechnology, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Madhya Pradesh, India.
³ ICMR - Regional Medical Research Centre, North East Region, Dibrugarh, Assam, India.
⁴ People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India.

Abstract

Background: India, with the largest population and second-highest type 2 diabetes mellitus (T2DM) prevalence, presents a unique genetic landscape. This study explores the genetic profiling of T2DM, aiming to bridge gaps in existing research and provide insights for further explorations.

Methods: We conducted a systematic review and meta-analysis of literature published up to September 2024 using databases like PubMed, Web of Science, Scopus, and Google Scholar to identify SNPs associated with T2DM in case-control studies within the Indian population. Data extraction followed a rigorously designed checklist independently verified by two reviewers. The quality of the studies assessed by utilizing Newcastle Ottawa scale, and heterogeneity through Cochran's Q, τ², H² and I ² statistics. Fixed effect and random effect model was employed for meta-analysis based on heterogeneity, and publication bias was assessed by funnel plot analysis, Egger's and Begg's statistical test. In SNPs with adequate studies meta-regression was used to assess source of heterogeneity. Statistical analyses were performed using Stata 18.0 software.

Findings: Our search identified 1309 articles, with 67 included in the systematic review and 35 in the meta-analysis. These 67 case-control studies, involving 33,407 cases and 30,762 controls, analyzed 167 SNPs across 61 genes. Of these, 89 SNPs mapped to 46 genes showed significant associations with T2DM risk (P < 0.05), including 67 linked to increased risk and 16 with protective effects. Geographical analysis highlighted inter- and intra-regional variations. Meta-analysis of 25 SNPs revealed 12 SNPs with high T2DM risk compatibility. TCF7L2 gene exhibited a strong compatibility with an overall OR of 1.44 (95% CI 1.36-1.52) and S-value 112.41, while TCF7L2 variants rs7903146 and rs12255372, with OR 1.56 (95% CI 1.43-1.66) and S-value 89.036, OR of 1.36 (95% CI 1.17-1.35) with an S-value of 15.45 respectively.

Interpretation: Our study highlights the importance of considering the diverse ethnic groups of India for development of targeted and effective T2DM management strategies.

Funding: Department of Biotechnology (DBT) and Indian Council of Medical Research (ICMR), Government of India.

Keywords: Case–control; India; Single nucleotide polymorphism (SNP); Susceptible gene; Type 2 diabetes mellitus (T2DM).