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Aim: The association of polymorphisms in the three genes of SOCS3, JAK2 and STAT3 with genetic susceptibility to type 2 diabetes mellitus (T2DM) was explored, and its interaction with environmental factors such as hypertension and triglycerides was analyzed. Methods: The Hardy–Weinberg balance test was used to analyze the random balance of genes in the population. The analysis of the association of SNPs with T2DM was performed using Pearson's chi-square test. Haplotype frequency distribution, SNPs-SNPs interaction and environmental factors were analyzed by chi-square test and logistic regression. Results: The genotype distribution of SNPs rs2280148 of the SOCS3 gene was statistically significant. The allele frequency distribution of SNPs (rs4969168/rs2280148) was statistically different. After covariate correction, the SOCS3 gene locus (rs4969168) showed an association with T2DM in additive model, while the rs2280148 locus showed an association with T2DM in all three models. The locus (rs10974914/rs10815157) allele and genotype frequency distribution of JAK2 were statistically significant. After covariate correction, two SNPs in the gene showed association with T2DM in both additive and recessive models. The distribution of genotype frequencies of SNPs rs1053005 locus in gene STAT3 was statistically significant between the two groups. In recessive genetic models, rs1053005 locus polymorphisms was associated with T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene as well as haplotype J2 (A G)/J 3 (G C) of the JAK2 gene were closely associated with T2DM. There was an interaction between SNPs rs4969168 and SNPs rs2280148 in the SOCS3 gene. There was an interaction between the SOCS3, JAK2 and STAT3 genes and hypertension/triglycerides. Conclusion: The SOCS3 and JAK2 genes may be associated with T2DM in the Chinese population, in which SNPs carrying the A allele (rs4969168)/G allele (rs2280148)/C allele (rs10815157) have a reduced risk of T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene and haplotype J2 (A G)/J 3 (G C) of the JAK2 gene may be influencing factor for T2DM. The interaction between SNPs rs4969168 and SNPs rs2280148 increases the risk of T2DM. Hypertension and triglycerides may interact with SNPs of T2DM susceptibility genes. [ABSTRACT FROM AUTHOR]

The aim of the present study is to explored the relationship between ADIPO signalling pathway and T2DM, to provide clues for further study of the pathogenesis of T2DM and to determine the possible drug targets. This study employed a case-control study design. Twenty-three single nucleotide polymorphisms (SNPs) of 13 genes in the selected ADIPO signalling pathway were genotyped by SNPscanTM kit. All statistical analysis was performed by SPSS 25.0, PLINK 1.07, R 2.14.2, Haploview 4.2, SNPstats, and other statistical software packages. In the association analysis based on a single SNPs, rs1044471 had statistical significance in the overdominant model without adjusting covariates. Rs1042531 had statistical significance in the overdominant model. Rs12718444 had statistical significance in the recessive model. There was a linkage disequilibrium between the loci within 9 genes, and the two loci in RXRA gene did not form blocks. Four kernel functions were used for SNPs set analysis based on ADIPO signalling pathway showed that there was no statistical significance whether covariates were added or not, P>0.05.According to our research results, it is found that some single nucleotide polymorphisms (ADIPOR2 rs1044471, PCK1 rs1042531, GLUT1 rs12718444) in the adiponectin signalling pathway may be associated with T2DM [ABSTRACT FROM AUTHOR]

Objective. This study is aimed at analyzing the relationship between leptin (LEP) signaling pathway and type 2 diabetes mellitus (T2DM) and at providing support for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. Methods. A case-control study was designed, including 1092 cases with T2DM and 1092 healthy controls of Chinese Han origin recruited from ten hospitals in Guangdong Province, Southern China. Twenty-three single nucleotide polymorphisms (SNPs) of 15 genes in LEP signaling pathway were genotyped by SNPscan™ kit. The Pearson chi-square test, Cochran-Armitage trend test, MAX3, and logistic regression were applied to analyze the association between single nucleotide polymorphism (SNP) and T2DM; unconditional logistic regression was used to analyze haplotype in LD block; and SNP set analysis based on logistic kernel machine regression was used to analyze pathway. All statistical analysis was performed by SPSS25.0, R2.14, Haploview4.2, SNPStats, and other statistical software packages. Results. In association analysis based on SNP, rs2167270 had statistical significance both in the adjusted and unadjusted covariate dominant model and in the unadjusted covariate overdominant model while it had no significant difference in the adjusted covariate overdominant model. Compared to GG genotype, rs2167270 of AG genotype had statistical significance in both the adjusted and unadjusted covariate codominant models. And rs16147 had statistical significance in robust test, stealth model and overdominant model, and adjusting and unadjusting covariate. This study found linkage disequilibrium existed between rs2167270 and rs4731426 of LEP, rs10889502 and rs17127107 of JAK1, rs2970847 and rs6821591 of PPARGC1A, rs249429 and rs3805486 of PRKAA1, rs1342382 and rs6588640 of PRKAA2, rs3766522 and rs6937 of PRKAB2, rs2970847 and rs6821591 of PRKAG2, and rs6436094 and rs645163 of PRKAG3. There was no positive finding with statistical significance from the unconditional logistic regression of the mentioned genes' haplotype of LD block. Conclusions. LEP signaling pathway association with T2DM remained to be confirmed in Chinese Han population, although rs2167270 and rs16147 were significantly associated with T2DM. [ABSTRACT FROM AUTHOR]

Chronic inflammation of adipose tissue may be one of the key factors contributing to the development of insulin resistance in T2DM adipose tissue. Transient receptor potential vanilloid type 4 (TRPV4) can be involved in a variety of cellular inflammatory responses. In this study, we evaluated the role of TRPV4 channelin in the T2DM adipose tissue inflammatory pathway. Based on the gene expression profiling data of the public database, bioinformatics methods were used to screen the target gene population of the TRPV4 channel protein involved in the regulation of T2DM fat cells. A mature adipocyte model was constructed to verify the expression level of target genes and to evaluate the regulatory effect of TRPV4 channel inhibition on target genes of inflammation-related pathways. In shTRPV4 adipocytes, 144 genes with downregulation expression were screened, a PPI network was constructed and a core module containing 15 genes was screened out, and the core genes were mainly enriched in the Toll-like receptor signaling pathway through enrichment analysis. Constructing a mature adipocyte model found that the TRPV4 inhibitor HC067047 inhibited the effect of upregulation of the expression level of the relevant gene in the signaling pathway. Our findings suggest that the expression of highly expressed pro-inflammatory cytokines and chemokines in T2DM adipose tissue decreases after inhibiting the expression of TRPV4 in adipocytes, suggesting that TRPV4 may become a potential drug target for the treatment of T2DM. • Gene expression data analysis showed an increase in TRPV4 expression in T2DM. • Inhibition of TRPV4 can reduce the production of pro-inflammatory cytokines. • This suggests that TRPV4 may be a potential drug target for the treatment of T2DM. [ABSTRACT FROM AUTHOR]