<p>TLR4 Polymorphisms (896A>G and 1196C>T) Affect the Predisposition to Diabetic Nephropathy in Type 2 Diabetes Mellitus</p>

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) is a disease with a steadily increasing incidence throughout the world. Some molecules regulating the innate immune responses such as tolllike receptor 4 (TLR4) have shown to be involved in late diabetic complications. This study aimed to investigate the association of TLR4 gene polymorphisms with clinicopathological aspects of T2DM in the Iranian population. Patients and Methods: Two TLR4 896A>G and 1196C>T polymorphisms were assessed in 100 T2DM patients and 100 healthy controls using sequence-specific primers PCR. Demographic, anthropometric, and biochemical parameters were obtained from the participants. Results: After logistic regression, in 1196C>T, a significant association was shown between diabetic nephropathy (DN) and CT genotype (P= 0.04, OR= 4.35, CI= (1.04-18.1)). TG level has increased significantly in both T2DM and control subjects with CT genotype (P= 0.027, OR= 1.005, 95% CI= (1.001-1.01)). For 896A>G variant, a significant association was also detected between AG genotype and increased oral glucose tolerance test (OGTT) level (P= 0.048, OR= 1.003, 95% CI= (1.00-1.005)). Conclusion: Although minor alleles of 1196C>T and 896A>G variants have not directly been associated with type 2 diabetes, by involving in the dysregulation of serum TG and blood sugar levels, they might increase the risk of DN.

Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients

“…32 In addition, minor alleles have not been directly linked to type 2 diabetes, but they may raise the risk of diabetic nephropathy through affecting levels of triglycerides and blood sugar. 33 The SARS-CoV-2 genome encodes four proteins; spike (S), membrane (M), envelope (E), and nucleocapsid (N). The virus invades host cells by interacting its S protein with the angiotensin-converting enzyme-2 (ACE-2) receptor on the host's cell membrane.…”

Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis

“…We reviewed the titles and abstracts, 773 articles were excluded. By reading the full text to exclude duplicate, non-English, non-Asp299Gly locus, original text cannot obtain genotype and allele frequency excluded 22, 7 articles were initially included [ 15 – 20 , 24 ]. Through data collation, 1 literature with no mutation in Asp299Gly site was not included in this meta analysis [ 24 ].…”

“…Through data collation, 1 literature with no mutation in Asp299Gly site was not included in this meta analysis [ 24 ]. Finally, 6 articles that met the inclusion criteria were included in this study [ 15 – 20 ], including 11 case–control studies. The main characteristics of the selected studies are listed in Table 1 , with a total of 11 studies of 1834 cases and 4069 controls for investigating the association between DMI and TLR4 Asp299Gly polymorphism.…”

“…Yin et al indicated that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with increased T2DM risk through a meta-analysis [ 13 ], whereas Chang et al pointed out some problems that still exist or need to be improved in the meta-analysis of Yin et al [ 14 ]. Several studies have shown that TLR4 gene polymorphism is associated with the occurrence of DMI, among which the research on TLR4 Asp299Gly is the hotspot [ 15 – 24 ]. Khaghanzadeh et al [ 15 ] showed that c.1196C > T and 896A > G variants might increase the risk of DR by involving in the dysregulation of serum lipid levels and hyperglycemia.…”

“…Several studies have shown that TLR4 gene polymorphism is associated with the occurrence of DMI, among which the research on TLR4 Asp299Gly is the hotspot [ 15 – 24 ]. Khaghanzadeh et al [ 15 ] showed that c.1196C > T and 896A > G variants might increase the risk of DR by involving in the dysregulation of serum lipid levels and hyperglycemia. Buraczynska et al [ 16 ] concluded that the G(rs4986790) polymorphism of TLR4 Asp299Gly allele increased the risk of DR. That is to say, a significant increase of G allele frequency was observed in DR compared to those without it in T2DM (OR = 2.12, 95% CI (1.43–3.12), p = 0.0002).…”