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

Zhang, Yuqi; Li, Huanhuan; Wang, Chenyi; Lv, Haihong; Fu, Songbo

doi:10.1186/s13098-022-00849-2

Cited by 7 publications

(3 citation statements)

References 40 publications

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“…A combined study of the SNPs rs11536889, rs4986790, and rs4986791 revealed that they may increase the risk of T2DM [63]. A recent meta-analysis evaluated the risk of diabetic microvascular complications and found that rs4986790 SNP was associated with T2DM, particularly in patients with diabetic retinopathy [64].…”

Section: Discussionmentioning

confidence: 99%

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Alkudmani,

Alshammary,

Ali Khan

2023

Cells

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Single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene have been documented in type 2 diabetes mellitus (T2DM) and other diseases in the Saudi population. We investigated the relationship between rs11536889, rs4986790, and rs4986791 SNPs in the TLR4 gene and T2DM in the Saudi population; 105 patients with T2DM and 105 healthy controls were analyzed. The TLR4 gene was amplified through PCR, followed by restriction fragment length polymorphism analysis for rs4986791 and Sanger sequencing for rs11536889 and rs4986790 SNPs. The clinical and biochemical characteristics were associated with T2DM (p < 0.05). The rs11536889, rs4986790, and rs4986791 SNPs in control subjects followed the Hardy–Weinberg equilibrium (p > 0.05). Alleles were associated with rs11536889, rs4986791, heterozygous codominant, and dominant models (p < 0.05). However, the rs4986790 SNP was not associated with T2DM (p > 0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol (HDLc) levels were associated with T2DM (p < 0.001). Analysis of variance showed that waist (p = 0.0005) and hip circumferences (p = 0.002) in rs4986790 and rs4986791 SNPs, in SBP (p = 0.001), DBP (p = 0.002), and HDLc levels (p = 0.003), were associated with T2DM subjects. T2DM was also associated with the haplotype (p < 0.001) but not with linkage disequilibrium. The gene–gene interaction was associated with the three SNPs studied in patients with T2DM according to the generalized multifactor dimensionality reduction model (p < 0.0001). Dendrogram and graphical depletion analysis revealed a moderate association in patients with T2DM. The results suggest that rs11536889 and rs4986790 SNPs are genotypically and allelically associated with T2DM in Saudi patients. Future functional studies are recommended to validate the genetic roles of these SNPs in the pathogenesis and progression of diseases.

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Section: Discussionmentioning

confidence: 99%

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Alkudmani,

Alshammary,

Ali Khan

2023

Cells

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“…Дослідження стверджують, що генетична схильність може бути одним із факторів, які викликають очні ускладнення ЦД2 [12][13][14]. Розглядаючи роль TLR4 в ДР, кілька дослідників зосередили увагу на асоціації поліморфізмів гена TLR4 й ризику розвитку ДР [14][15][16]. Так, виявлено, що поліморфізми гена TLR4 асоціюються з підвищеним ризиком серцево-судинних захворювань і діабетичної ретинопатії в пацієнтів із ЦД2 [15,16], тоді як за іншими даними мають протективний ефект [17].…”

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Association of TLR4 rs1927911 polymorphism with diabetic retinopathy and diabetic macular edema in type 2 diabetic patients

Rykov,

Galytska,

Zhmuryk

et al. 2024

Oftalmol Zh

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“…Генетична схильність є одним із головних чинників, що викликають очні ускладнення ЦД2 [6,7]. Досить добре описа-на асоціація поліморфізмів гена TLR4 і ризику розвитку ДР, при цьому деякі поліморфізми не мають зв'язку, інші збільшують ризик, а деякі ризик ДР зменшують [8][9][10].…”

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TLR4 GENE POLYMORPHISM rs2149356 IN TYPE 2 DIABETES - POSSIBLE RELATIONSHIP WITH DIABETIC MACULAR EDEMA

Ivanyuta

2023

Med. Sci. of Ukr.

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Background. Polymorphisms in the non-coding regions of the TLR4 gene are known to be associated with the risk of ocular complications of type 2 diabetes (T2DM), with some polymorphisms having no association, others increasing the risk, and some reducing the risk of complications. Aim: to establish the association of the TLR4 gene polymorphism rs2149356 with diabetic retinopathy (DR) and diabetic macular edema (DME) in T2DM. Materials and methods. The study included 81 patients (81 eyes) with T2DM, in whom, according to the guidelines of the American Academy of Ophthalmology (2002), DR and DME were detected, the control group consisted of 50 patients (50 eyes) with T2DM, normalized carbohydrate metabolism, DR 0 (no retinopathy) and absent DME. Genotypes of rs2149356 were determined by real-time polymerase chain reaction using the Gene Amp® PCR System 7500 amplifier (Applied Biosystems, USA) and TaqMan Mutation Detection Assays Life-Technology (USA). MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used for statistical research. Results. In this study, no association of the genetic polymorphism rs2149356 of the TLR4 gene with the development of DR and DME in T2DM was found (p=0.326). Stratification by stages of DR showed no dependence of the distribution of genotypes, while according to the degree of DME, the distribution of genotypes was definitely different in DME 3. Thus, among the carriers of the ancestral genotype G/G, none of DME 3 was found, the borderline level of the total retinal volume (TRV) was 6.7 mm3, above which DME 1 or DME 2 was determined. All carriers of the heterozygote G/T had DME 3, and for carriers of the minor homozygote T/T, two threshold values of TRV were determined: above 6.7 mm3, DME 1 or DME 2 was determined, and higher than 8.7 mm3 – DME 3. Analysis of the relationship between the rs2149356 TLR4 and the phenotype of patients showed greater central retinal thickness and TRV in heterozygous and minor homozygous T/T carriers, which corresponded to greater retinal damage compared to ancestral homozygous G/G carriers (p<0.001). Conclusion. Data were obtained on the association of diabetic retinal damage with the rs2149356 TLR4 – retinal edema was more pronounced in carriers of the T allele.

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

Cited by 7 publications

References 40 publications

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Molecular Effect of Variants in Toll-like Receptor 4 Gene in Saudi Patients with Type 2 Diabetes Mellitus

Association of TLR4 rs1927911 polymorphism with diabetic retinopathy and diabetic macular edema in type 2 diabetic patients

TLR4 GENE POLYMORPHISM rs2149356 IN TYPE 2 DIABETES - POSSIBLE RELATIONSHIP WITH DIABETIC MACULAR EDEMA

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