Long Noncoding RNA GUSBP3 And SAM4 Function As Potential Diagnostic Biomarkers of Type 2 Diabetes Mellitus In Kazak Populations In The Xinjiang Region of China

Abstract

Background: The pathogenesis of T2DM is influenced by a combination of genetic and environmental factors, among which LncRNAs have a huge impact on diabetes.In this study, we investigated the diagnostic value of lncRNA GUSBP3 and lncRNA SAM4 for T2DM in Kazakhs in Xinjiang. Methods: In this study, differentially expressed lncRNAs and mRNAs were screened by microarray analysis microarray in a Kazakh population in Xinjiang, and the expression of two candidate lncRNAs (lnc-GUSBP-3 and lnc-SAM-4) was further validated by quantitative real-time polymerization chain reaction (qRT-PCR).Meanwhile, GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Spearman’s correlation analysis was used to elucidate the correlation between lnc-GUSBP-3 and lnc-SAM-4 expression and metabolic characteristics. We found that the expression of lnc-GUSBP-3 and lnc-SAM-4 was up-regulated in the T2DM group compared to healthy controls. Multivariate logistic regression analysis showed that DBP, FIns and lnc-GUSBP3 were associated with T2DM susceptibility.In addition, ROC curves were used to evaluate the diagnostic potential of lnc-GUSBP3 and lnc-SAM4. Results: We conducted a microarray analysis of PBMC collected from patients with T2DM and healthy controls, all of Kazakh origin. In the microanalysis, we identified 89 differentially expressed lncRNAs, and 147 differentially expressed mRNAs. real-time quantitative reverse transcription polymerase chain reaction analysis of peripheral blood mononuclear cell (PBMC) samples from T2DM patients and healthy controls from the Xinjiang Kazakh population revealed significantly increased levels of lncRNAs GUSBP3 and SAM4 in T2DM patients. Logistic regression analysis revealed that lncRNA GUSBP3 expression correlated negatively with FIns, but positively with creatinine and uric acid (UA). Furthermore, lncRNA SAM4 expression correlated negatively with low-density lipoprotein cholesterol levels, but positively with UA. The area under the receiver operating characteristic curve values for lnc-GUSBP3 and lnc-SAM4 were 0.789 (95% CI = 0.672–0.906) and 0.741 (95% CI = 0.616–0.866), respectively. Conclusion: There were significant changes in lncRNA and mRNA in Kazakh T2DM patients. LncRNA-GUSBP3 and lncRNA-SAM4 may serve as potential diagnostic biomarkers for T2DM in Kazakhs in Xinjiang.