A SYSTEMATIC REVIEW OF SNP POLYMORPHISM STUDIES IN SOUTH ASIAN POPULATIONS: IMPLICATIONS FOR DIABETES AND AUTOIMMUNE DISORDERS

Abstract

Single nucleotide polymorphisms (SNPs) represent the most prevalent form of genetic variation in the human genome and are widely recognized for their role in influencing susceptibility to complex diseases, including type 2 diabetes mellitus (T2DM) and autoimmune disorders such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Given their rich genetic heterogeneity, distinct evolutionary histories, and high burden of metabolic and immune-related diseases, South Asian populations offer a compelling landscape for exploring SNP-disease associations. However, global genomic research continues to underrepresent these populations, resulting in limited population-specific insights and potential misclassification of disease risk. This study conducted a comprehensive integrative review to synthesize existing empirical evidence on SNP polymorphism studies focused on diabetes and autoimmune disorders across South Asian countries—namely India, Bangladesh, Pakistan, Nepal, and Sri Lanka. A total of 114 peer-reviewed research articles, published between 2000 and 2024, were systematically identified, screened, and analyzed according to integrative review guidelines. The findings revealed consistent associations between several SNPs and disease phenotypes, including TCF7L2 (rs7903146), FTO (rs9939609), and SLC30A8 (rs13266634) in relation to T2DM, and HLA-DRB1, PTPN22, STAT4, and CTLA4 in the context of autoimmune diseases. While many of these loci mirrored global GWAS findings, their allele frequencies and effect sizes varied markedly across South Asian subpopulations, with notable differences between ethnic, linguistic, and caste-based groups. Despite these insights, the review identified key methodological and infrastructural gaps, including reliance on low-throughput genotyping techniques, limited sample sizes, underutilization of SNP–SNP and gene–environment interaction models, and minimal integration of functional annotation. Clinical translation remains nascent, with very few studies advancing toward the development of population-specific polygenic risk scores or diagnostic tools. Moreover, tribal, rural, and marginalized communities remain largely unrepresented in genomic research, limiting equitable knowledge generation. Ethical oversight, informed consent processes, and genomic literacy were also found to be inconsistently addressed. This review underscores the need for comprehensive, methodologically rigorous, and ethically inclusive SNP research in South Asia. Expanding genomic reference panels, investing in high-throughput technologies, and fostering collaboration across national and regional institutions will be critical for advancing precision medicine and reducing health disparities in this genetically diverse and populous region.