Genetic Variation Of IGFBP7Is Associated With Metabolic Syndrome

Insulin-like growth factor with high homology compared with insulin is a kind of regulation factor, which can promote cell proliferation and differentiation. The insulin-like growth factor (IGF) system is a complex network. It is composed of ligands, receptors, IGF-binding proteins (IGFBPs) and IGFBP proteases. In recent years, there are more and more attentions to the function of IGF system.IGFBPs are the important parts of IGF system, which can regulate the function of IGFs by binding to the IGFs. There are15members in the IGFBP family. IGFBP1-6, these six IGFBPs have high binding affinities to IGFs, but IGFBP7-15which have lower binding affinities to IGFs than IGFBP1-6, are named insulin like growth factor binding protein-related proteins (IGFBP-rps). It means these members may have some other functions. There are more reports about IGFBP7. Compared with IGFBP1-6, the binding affinity to IGF1and IGF2of IGFBP7is about5-fold and20to25-fold lower, but the binding affinity to insulin of IGFBP7is about500-fold higher. The insulin combined with IGFBP7will lose or reduce the biological effects. It decreases the insulin sensitivity of our body and leads to insulin resistance. It is suggested that IGFBP7could inhibit the effect of insulin by competitively binding with insulin and preventing insulin from binding with its receptor which would lead to insulin resistance. IGFBP7may be the key factor about insulin resistance. The expression level of IGFBP7 may have an effect on insulin sensitivity, so it may become a new biomarker of insulin resistance and a new point for the research about metabolic syndrome and other chronic disease.There are many researches and reports about the association between the epigenetics and the expression of IGFBP7. It is just a part of mechanism about regulating the expression of IGFBP7. Another mechanism is genetic variation. Single nucleotide polymorphism (SNP), which has an effect on the functions of gene, is associated with transcription factor binding sites, mRNA slicing, amino acid sequence and non-coding RNA. IGFBP7is located in4q12-13and it is about79206bps long. It contains5exons and it is about30kDa. There are about199SNPs in the area of3000bps upstream to3000bps downstream in IGFBP7gene. It is reported that rs4075349and rs11573014which are in the promoter area of IGFBP7, are associated with head and neck cancer.There are few reports about the genetic variation of IGFBP7. It has never been reported that the genetic variation of IGFBP7is associated with insulin resistance and metabolic syndrome. Our study aims to identify whether the genetic variation of1GFBP7is associated with insulin resistance and metabolic syndrome. We found rs4075349and another new SNP+69622A/C in Chinese people (MAF>0.05) by PCR and sequencing. In a case-control study of200patients with metabolic syndrome (MS) and200controls of Chinese, we investigated associations between two SNPs (rs4075349and+69622A/C) and the risk of insulin resistance and metabolic syndrome. A significantly higher risk of metabolic syndrome was observed in those subjects carrying AG (adjusted OR=1.575,95%CI=1.029-2.413) and GG+AG (adjusted OR=1.552,95%CI=1.041-2.313) genotypes than those carrying the AA genotype for the rs4075349, but not for the+69622A/C SNP (P>0.05). A significantly higher risk of insulin resistance was also observed in those subjects carrying GG+AG (adjusted OR=1.515,95%CI=1.005-2.283) genotypes than those carrying the AA genotype for the rs4075349. These are also not observed for the+69622A/C SNP (P>0.05). In our study, we observed that the genetic variation of IGFBP7was not associated with the level of IGFBP7in serum. We also investigated whether there was any difference in the level of IGFBP7in serum between cases and controls (insulin resistance and metabolic syndrome), but we found there was no difference in the level of IGFBP7in serum between cases and controls (P>0.05). From above results, we can get followingconclusions:1. rs4075349is associated with insulin resistance and metabolic syndrome. Allele G is associated with increased risk of insulin resistance and metabolic syndrome.2. genetic variation of IGFBP7is not associated with the level of IGFBP7in serum.