The Association Of RANTES And Its Receptor CCR5 Gene Polymorphism And Expression Level With Type 2 Diabetes Mellitus In Kunming Han Population

Objectives:To explore the association of RANTES gene promoter region-28(rs2280788)C/G polymorphism and its receptor CCR5 gene promoter region 59029(rs1799987)A/G polymorphism and their expression levels with Type 2 diabetes(Type 2 diabetes mellitus,T2DM)in Kunming Han population,and the influencing factors of RANTES,CCR5 expression levels and T2DM.Methods:The general data and peripheral venous blood of 92 Han people with normal blood glucose(NC group)and 97 Han T2DM patients(DM group)in Kunming area were collected.Biochemical indexes were detected by automatic biochemical analyzer.The levels of CCR5 on monocytes and lymphocytes and plasma RANTES were determined by flow cytometry.Polymorphisms of RANTES gene rs2280788 and CCR5 gene rs 1799987 were detected by TaqMan real-time quantitative PCR.Chi-square goodness-of-fitting test was used to test whether the genotype distribution of the selected samples complied with Hardy-Weinberg genetic equilibrium law.SPSS 26.0 was used for statistical analysis.Normal measurement data was expressed as mean ± standard deviation(x±s),non-normal measurement data was expressed as median(lower quartile,upper quartile),and enumeration data was expressed as rate.Two independent samples t-test was used for the comparison of normal measurement data between two groups,and two independent samples rank sum test was used for the comparison of non-normal measurement data between two groups.The comparison of normal measurement data among three groups was performed by the One-Way analysis of variance,the pairwise comparison was performed by the LSD-t test,and the non-normal measurement data was performed by the Kruskal-Wallis test.Enumeration data were compared using χ2 test.Pearson correlation analysis was used for the correlation analysis of normal measurement data,and Spearman correlation analysis was used for the correlation analysis of non-normal measurement data.Unconditional Logistic regression was used to analyze the influencing factors of diabetes.Multifactor dimensionality reduction(MDR)was used to analyze the interaction among the gene polymorphisms of RANTES and its receptor and environmental factors in the occurrence of T2DM in Han nationality in Kunming.P<0.05 was considered statistically significant(P<0.017 was considered statistically significant when the three groups were compared in pairs).Results:1.The FPG,HbAlc,waist circumference,BMI,systolic blood pressure,and the level of TG of DM group were higher than those of NC group(P<0.05),the level of TC,HDL of DM group were lower than those of NC group(P<0.05).There were no statistically significant differences in age,gender,diastolic blood pressure and LDL level between the two groups(P>0.05).2.There were no significant differences in genotype frequency and A/G allele frequency of CCR5 rs 1799987,as well as the genotype frequency and C/G allele frequency of RANTES rs2280788 between NC group and DM group(P>0.05).3.Plasma RANTES level in DM group was significantly lower than that in NC group(P<0.05),the difference was derived from T2DM patients using insulin and those with normal blood glucose(P<0.017).The expression level of CCR5 on monocytes and lymphocytes in DM group was higher than that in NC group(P<0.05).4.There was no significant difference in the expression level of CCR5 on monocytes and lymphocytes among different CCR5 rs 1799987 genotype groups(P>0.05),there was no significant difference in plasma RANTES level between different RANTES rs2280788 genotype groups(P>0.05).5.RANTES level was positively correlated with age and TC level in the Han population in Kunming area,and negatively correlated with the course of diabetes and HbA1c.The level of CCR5 on monocytes was positively correlated with the number of years of drinking,HbA1c,and the course of diabetes mellitus,and negatively correlated with TC level.The level of CCR5 on lymphocyte was positively correlated with the duration of diabetes mellitus,the number of years of smoking and HbAlc,and negatively correlated with LDL,TC and HDL level(P<0.05).6.Multivariate Logistic regression analysis showed that CCR5 expression level on lymphocyte surface(OR:1.082,95%CI:1.031～1.135),family history of diabetes mellitus(OR:6.464,95%CI:2.634-15.866)and hypertension(OR:4.182,95%CI:1.836～9.527)were independent risk factors for T2DM in Kunming Han nationality(P<0.05).7.MDR showed that there was an interaction between CCR5 rs 1799987 and RANTES rs2280788(the testing balance accuracy was 0.5314,the training balance accuracy was 0.5820,and the cross validation consistency was 10/10,P<0.05,OR:2.0465,95%CI:1.1118-3.7672);There was an interaction between hypertension and central obesity(the testing balance accuracy was 0.7031,the training balance accuracy was 0.7031,the cross validation consistency was 10/10,P<0.001,OR:8.1640,95%CI:3.8745-17.2026);No interaction was found between CCR5 rs1799987 and environmental factors or between RANTES rs2280788 and environmental factors(P>0.05)。Conclusions:1.RANTES gene promoter region-28(rs2280788)C/G polymorphism and CCR5 gene promoter region 59029(rs1799987)G/A polymorphism may not be associated with T2DM in Han nationality in Kunming,and may not be the main influencing factors of their expression levels.2.The higher the level of CCR5 on the lymphocyte,the higher the risk of T2DM.The level of Plasma RANTES and CCR5 on monocytes may not be associated with the occurrence of T2DM.3.RANTES level was positively correlated with age and TC level in the Han population in Kunming area,and negatively correlated with the course of diabetes and HbA1c.The level of CCR5 on monocytes was positively correlated with the number of years of drinking,HbA1c,and the course of diabetes mellitus,and negatively correlated with TC level.The level of CCR5 on lymphocyte was positively correlated with the duration of diabetes mellitus,the number of years of smoking and HbAlc,and negatively correlated with LDL,TC and HDL level.4.Family history of diabetes and hypertension were the independent risk factors for T2DM in the Han population in Kunming.5.In the occurrence of T2DM,there are interactions between two SNPs of RANTES gene promoter region-28(rs2280788)and CCR5 gene promoter region 59029(rs 1799987),as well as between hypertension and central obesity,which may increase the risk of T2DM in the Han population in Kunming.