Al-Razem Fawzi, Iqnaibi Enas B, Abu Rmeileh Razan A, Ideis Lara I
College of Medicine and Health Sciences, Palestine Polytechnic University, P.O. Box 198 Hebron, Palestine.
Applied Biology Program, College of Applied Sciences, Palestine Polytechnic University, P.O. Box 198 Hebron, Palestine.
Endocr Metab Immune Disord Drug Targets. 2025;25(9):675-681. doi: 10.2174/0118715303301789240826113528.
Toll-like Receptor 4 (TLR4) plays critical roles in innate immunity and several other pathological responses, including a possible role in the susceptibility to Type 2 Diabetes Mellitus (T2DM). Understanding the relationship between TLR4 polymorphism and T2DM is necessary to evaluate the role of innate immunity in diabetes.
This study was conducted to evaluate the potential association between three TLR4 SNPs (SNP ID rs11536858, rs4986790, and rs1927914) and risk susceptibility to T2DM in a crosssection of the Palestinian population.
A total of 96 individuals including 50 T2DM patients participated in this study. The data were analyzed according to the TLR4 allelic variation results. DNAs were extracted from blood samples collected from the T2DM patients and their matched healthy controls and used to evaluate possible associations between the TLR4 SNP variations and T2DM. The genotypes of TLR4 polymorphisms were analyzed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
Three allelic variations were detected in the participating individuals. The distribution of alleles between T2DM and healthy controls in the three SNPs did not show significant differences, even though some variations tended to favor certain alleles. To look at potential associations of TLR4 gene polymorphisms with the risk of T2DM development, we analyzed the allelic variation in both T2DM patients and health controls. The rs4986790 TLR4 SNPs showed a significant association with T2DM. There were 20% heterozygous alleles in T2DM patients compared to 4.35% in healthy controls with Odds Ratio (OR) = 5.26 and 95% CI = 1.08, 25.6 (P = 0.0252), indicating the AG allele to be a risk factor. Both rs11536858 and rs1927914 alleles demonstrated a potential association of their allelic variations as either a protective or a highrisk factor.
Our data have indicated that TLR4 rs4986790, rs1927914, and rs11536858 may play a potential role in innate immunity and susceptibility risk to diabetes and can be potential targets for therapeutic drugs.
Toll样受体4（TLR4）在先天免疫及其他几种病理反应中发挥关键作用，包括在2型糖尿病（T2DM）易感性中可能发挥的作用。了解TLR4基因多态性与T2DM之间的关系对于评估先天免疫在糖尿病中的作用至关重要。
本研究旨在评估巴勒斯坦人群中三个TLR4单核苷酸多态性（SNP ID rs11536858、rs4986790和rs1927914）与T2DM风险易感性之间的潜在关联。
共有96人参与本研究，其中包括50名T2DM患者。根据TLR4等位基因变异结果对数据进行分析。从T2DM患者及其匹配的健康对照者采集的血液样本中提取DNA，用于评估TLR4 SNP变异与T2DM之间的可能关联。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析TLR4多态性的基因型。
在参与研究的个体中检测到三个等位基因变异。在这三个SNP中，T2DM患者与健康对照者之间等位基因的分布没有显示出显著差异，尽管某些变异倾向于某些等位基因。为了研究TLR4基因多态性与T2DM发生风险的潜在关联，我们分析了T2DM患者和健康对照者的等位基因变异。TLR4 SNP rs4986790与T2DM显示出显著关联。T2DM患者中有20%的杂合等位基因，而健康对照者中为4.35%，优势比（OR）=5.26，95%置信区间=1.08，25.6（P=0.0252），表明AG等位基因为风险因素。rs11536858和rs1927914等位基因的变异均显示出作为保护或高风险因素的潜在关联。
我们的数据表明，TLR4 rs4986790、rs1927914和rs11536858可能在先天免疫和糖尿病易感性风险中发挥潜在作用，并且可能成为治疗药物的潜在靶点。
