Toll-like Receptor 9 Gene in the Development of Type 2 Diabetes Mellitus in the Saudi Arabian Population

SIMPLE SUMMARY: The TLR9 gene is known to be a major element in an innate immune system. The relation between TLR9 and diabetes is connected via chronic inflammation, which affects the β-cell function. Previous studies on diabetes were with rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene, and there are no direct studies. The prevalence of T2DM was expanding in Saudi Arabia. One of the foot ulcer infections in diabetic individuals is linked to the relationship between infection and diabetes. Individuals who had a COVID-19 infection are at an increased risk of developing chronic diseases, such as diabetes; this has been observed in Saudi Arabia. We design this study between rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene and T2DM in the Saudi population. The current study results confirmed rs187084 and rs5743836 SNPs were associated in the Saudi population. This indicates that they play a role in the Saudi population. ABSTRACT: Diabetes mellitus is a complex disease with a wide range of manifestations. Diabetes, notably type 2 diabetes mellitus (T2DM), is becoming more common in Saudi Arabia as a result of obesity and an aging population. T2DM is classified as a noncommunicable disease, and its incidence in the Saudi population continues to grow as a consequence of socioeconomic changes. Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus. Previous studies have documented the relationship between different SNPs in the TLR9 gene in different forms of diabetes. As a result, the purpose of this study was to investigate the relationship between rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene among T2DM patients in the Saudi population. This was a case-control study that included 100 T2DM cases and 100 control subjects. The three SNPs were identified in the study population (n = 200) using polymerase chain reaction (PCR), restriction enzymes for rs352140, and Sanger sequencing for rs187084 and rs5783836. Next, statistical analyses were performed using various software to determine the association between the SNPs and T2DM. rs187084 and rs5743836 were associated with an increased risk of T2DM development. rs187084 and rs5743836 allelic frequencies were associated with a 3.2 times increased risk of T2DM development (p < 0.05). DBP was associated with T2DM (p = 0.02). rs187084 was associated with TC and HDLc; rs352140 was associated with DBP, HbA1c, and HDLc; rs5743836 was associated with waist (p < 0.05). The CGT haplotype was strongly associated with T2DM (p < 0.003). Gene–gene interaction, graphical presentation, and dendrogram showed the strong association with T2DM patients (p < 0.05). This study concluded that rs187084 and rs5743836 were strongly associated with T2DM in Saudi Arabian patients. This study provides further evidence that SNPs in the TLR9 gene play a significant role in T2DM development in a Saudi community.