Correlation Between IGFBP7 With Metabolic Syndrome And Insulin Resistance

Backgrounds and ObjectivesMetabolic syndrome(MetS)is a group of obesity,hyperglycemia(diabetes or glucose regulation damage),dyslipidemia and hypertension,such as the onset of clinical manifestations that seriously affect the health,and a combination of risk factors that are interrelated in metabolism,increasing the risk of diabetes,cardiovascular disease,stroke,and certain cancers.The prevention and control research of metabolic syndrome and its related chronic disease has become one of the most important aspects of disease control in China.The predominant underlying mechanism of MetS is insulin resistance(IR).Additionally,previous studies have shown that insulin-like growth factor binding protein 7(IGFBP7)has high affinity of binding with insulin,which indicated related to the occurrence of insulin resistance.The heritability of MetS and IR is from 30%to 50%,which means genetic factors are involved in the occurrence and development of MetS and IR.We hypothesized that the genetic variation of IGFBP7 affects gene expression and function,which is associated with the risk of MetS and IR.This study is to investigate the relationship between serum protein IGFBP7 levels with MetS and IRin a case-control design study based on a cross-sectional population,to reveal the role of the genetic variation of IGFBP7 in the development of MetS and IR.The results provide a new marker for the evaluation of MetS and IR,and help for intervention of MetS and IR.Material and MethodsAn epidemiological survey was conducted in the cross-sectional population.We investigated the serum protein IGFBP7 level,using the HOMA-IR index to evaluate the insulin sensitivity.In order to evaluate the relationship between serum protein IGFBP7 level with MetS and IR.Screening SNPs related with serum protein IGFBP7,and replicating in eQTL database,to explore the SNPs that could regulate the expression of IGFBP7(Expression SNP,eSNP);Analyzing the relationship between the genetic variation of IGFBP7 with MetS and IR,screening SNPs related with MetS and IR(Pheno SNP,phSNP);Screening of co-SNPs associated with gene expression and disease phenotype by integrating eSNPs and phSNP;Focusing on the change of the relationship between co-SNPs with MetS and IR,before and after adjusted by serum protein IGFBP7 level,to find SNPs which affects MetS and IR by regulating the expression of IGFBP7.ResultsWe found that the median level of serum IGFBP7 in MetS was 45.80 ng/ml(P25:36.50;P75:59.05),significantly higher than that in the control group 35.80 ng/ml(28.70,46.40)(P<0.001);The median level of serum protein IGFBP7 in the insulin resistance group was 40.45 ng/ml(31.83,52.45),higher than that of insulin-sensitive group 38.25 ng/ml(30.30,50.53)(P<0.05).The risk of MetS with high serum protein IGFBP7(?35.80 ng/ml)was 2.758 times(OR = 2.758,95%CI = 2.308-3.297)for low serum protein IGFBP7 group(<35.80 ng/ml).Also,the risk of IR in high serum protein IGFBP7 group was 1.240 times(OR = 1.240,95%CI =1.055-1.458)for the low protein IGFBP7 population.The serum protein IGFBP7 is associated with metabolic components(HDL-C,LDL-C,WHR).Compared with that of carriers with the major allele of rs13141016 or rs4865174,the protein serum IGFBP7 level of carriers with the minor allele of rs13141016 or rs4865174 were lower(rs4865174:?=-0.023,P = 0.021;rs 13141016:? =-0.011,P = 0.044);In GTEx,the genetic variation of rs13141016 was related with mRNA levels of transformed fibroblasts cells,visceral omentum adipose,whole blood,breast and subcutaneous adipose;the genetic variation of rs13141016 was related with mRNA levels of heart.Compared with that of carriers with the major allele of rs13141016 or rs4865174,the risk of MetS and IR of carriers with the minor allele of rs 13141016(? ?-0.019,P= 0.042)or rs4865174(? =-0.037,P = 0.031)were lower;In MAGIC database,the genetic variations of rs13141016 and rs4865174 were related with insulin.The relationships between rs 13141016 and rs4865174 with MetS and IR were no more significant after additionally adjusted by serum protein IGFBP7;Rs4865174 and rs 13141016 may affect gene expression for difference ability of allele on binding transcription factor;Rs13141016 was also located in elite enhancer GH04F057070;Rs4865174 and rs13141016 may regulate gene expression by affecting the transcription factor binding sequence or affecting the enhancer effect,which were also related with MetS and IR.ConclusionsSerum protein IGFBP7 is associated with of MetS and IR.The gene IGFBP7 can affect the risk of MetS and IR by regulating gene expression.