Heightened Frequency of Innate Immunity Risk Alleles in South Indian Diabetics with Urinary Tract Infections

Urinary Tract Infections are an emerging public health concern among individuals with diabetes mellitus, particularly in South Asia where high disease burden, genetic diversity and increasing drug resistance contribute to the progressive increase in burden. While metabolic and clinical risk factors are well studied, the role of host innate immune genetic variations in shaping UTI susceptibility among diabetics remains poorly understood. This case-control study evaluated functional polymorphisms in key innate immunity genes, TLR4 (rs4986790, rs4986791), MBL2 (rs1800450) and LTA (rs909253), in 70 T2D patients with UTI and 70 T2D patients without UTI. Genotyping was performed using 5'-hydrolysis probe assay. Across all the four SNPs, the risk allele consistently showed a higher frequency among T2D patients with UTI, indicating a directional trend suggestive of cumulative susceptibility. Also, a strong and significant protective association was observed for the LTA rs909253 'G' allele, which was less frequent in cases than controls. This low-inflammatory 'AA' genotype was also markedly enriched among rUTI cases compared to controls. Clinically, 34.3% of cases experienced rUTIs. This observed directional increase of risk alleles across all four innate immunity SNPs, along with the protective role of LTA rs909253 'G' allele, highlights cumulative host genetic modulation of UTI risk in T2D and supports translational use of genetic profiling in infection risk prediction.