| Objective: Type 2 diabetes is a kind of chronic inflammatory metabolic disease, thus it may cause the damages to many organs. However, the pathogenesis of type 2 diabetes is still unclear. TLR signaling pathways are involved in many inflammatory response. The NF-κB pathway which was mediated by TLRs has been proved to play an important role in the developing of diabetes, but the associations between the genes of TLR pathway and type 2 diabetes vascular complications have not been defined any more. The aim of our research is to reveal the relationships of the single nucleotide polymorphism of TLR2, TRAF3, NLRX1 and the vascular complications of T2 DM.Method:(1) We use the case-control study design and establish 3 paired compared groups: single type 2 diabetes vs. diabetes with microvascular lesion; single type 2 diabetes vs. diabetes with large vascular lesions; and single type 2 diabetes vs. diabetes with both microvascular lesion and large vascular lesions. There are 120 people in single type 2 diabetes, 176 people in diabetes with microvascular, 51 people in diabetes with large vascular lesions, and 105 people in diabetes with both microvascular lesion and large vascular lesions.(2) The clinical information of the 4 group patients was collected which conclude sex, age, BMI, the family history, smoking, drinking, Hb A1 c, TC, TG, HDL-C and LDL-C.(3) We screen the SNP locus on the basis of biological database.(4) We estimate the association between TLR2, TRAF3, NLRX1 and diabetes complications by statistical analysis.Results:(1) We finally selected 9 SNPs in 3 genes, and they are TLR2 rs1898830, TLR2 rs4696480 TLR2 rs3804099, TLR2 rs3804100, TRAF3 rs2144826, TRAF3 12435483, TRAF3 rs3803286, NLRX1 rs10790286 and NLRX1 rs561830.(2) After adjusting the age, sex and BMI factors, the TT genotype in NLRX1 rs561830 is associated with microvascular lesions(TT vs. CC, OR=2.20, 95%CI: 1.02-4.74, p=0.044). The AA genotype in TLR2 rs1898830 may increase the risk of having large vascular lesions in T2 DM patients(AA vs. AG+GG OR=2.46, 95%CI:1.03-5.86, p=0.043). The AA genotype in TLR2 rs1898830 is associated with people in diabetes having both microvascular lesion and large vascular lesions(AA vs. GG OR=3.28, 95%CI:1.23-8.79, p=0.018; AA vs. AG+GG OR=2.28. 95%CI:1.16-4.46, p=0.017). The AA genotype in TLR2 rs4696480 will increase the risk of having both microvascular lesion and large vascular lesions to those T2 DM patients(AA vs. TT, OR=3.56, 95%CI:1.35-9.40, p=0.011; AA vs. AA+AT, OR=2.56, 95%CI:1.32-4.98, p=0.006). In TRAF3 rs2144826, people with T2 DM who carry the AA genotype will increase the risk of having both microvascular lesion and large vascular lesions(AA vs. GG, OR=16.60, 95%CI: 1.52-181.11, p=0.021; AA vs. AG+GG, OR=15.89, 95%CI: 1.47-171.42, p=0.023). The analysis also show relevance on NLRX1 rs561830 TT genotype and concurrent of microvascular large vascular lesions(TT vs. CC, OR=3.39, 95%CI:1.28-8.99, p=0.014), and the T2 DM patient who carry the TC genotype and TT+TC genotype will increase the risk of both microvascular lesion and large vascular lesions(TC vs. CC, OR=2.66, 95%CI: 1.30-5.44, p=0.007; TT+TC vs. CC, OR=2.82, 95%CI:1.43-5.58, p=0.003).Conclusion: The genes of TLR2, NLRP3 and NLRX1 which could regulated in TLR2 signaling pathways may increase the risk of T2 DM vascular complications. |
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