IMPACT OF GENETIC DIVERSITY OF TLR4 (RS1927911) ON GLYCATED HEMOGLOBIN AND INFLAMMATORY LOAD IN IRAQI TYPE 2 DIABETIC PATIENTS

Abstract

Diabetes mellitus (DM) is a multifaceted metabolic disorder characterized by hyperglycemia, which has consequences that reduce quality of life and increase mortality rates. Toll-like receptor 4 (TLR4) is a key mediator of innate immune activation and has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene have been documented in type 2 diabetes mellitus (T2DM). Aim: This study investigates the association between the rs1927911 SNP in the TLR4 gene and T2DM in the Iraqi population. Methods: A case-control study recruited 300 type 2 diabetic Iraqi patients; 150 with dyslipidemia and 150 without served as the control group. Numerous metabolic and inflammatory analytes were determined by standard methods. Allele specific polymerase chain reaction (AS-PCR) was used to genotype TLR4 at rs1927911. Results: Fasting serum glucose (FSG), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and C-reactive protein (CRP) were significantly higher in the patient group than in the control group. In contrast, HDL-C decreased significantly during a comparable assessment. Genotyping analysis revealed an insignificant association with dyslipidemia. However, under the dominant genetic model, individuals carrying the G allele (G/A + G/G) exhibited significantly lower HbA1c levels than those with the A/A genotype (β = −2.15, 95% CI: −3.51 to −0.80, P = 0.002), indicating that the A/A genotype was associated with elevated HbA1c concentration. Other associations with FSG, TG, TC, LDL-C, HDL-C, TNF, and CRP were not significant after adjustment. Conclusion: The TLR4 rs1927911 polymorphism was not associated with diabetic dyslipidemia or inflammatory markers (TNF and CRP), but was significantly associated with HbA1c, suggesting a role in glycemic regulation rather than inflammation.