Association Of Rs2788 Polymorphism Of ERp57 Gene With Metabolic Syndrome In A Chinese Han Population

BackgroundRecently,there is growing interests in shared metabolic disorders of obesity,diabetes and cardiovascular disease(CVD),leading to the concept of metabolic syndrome(MetS).At present,the global prevalence of MetS is increasing year by year.A study has shown that the prevalence of MetS among Chinese adults is 11.0%between 2010 and 2012.The high prevalence rate of MetS has brought great economic and public health burden to the development of society,which urgently needs our attention.The pathogenesis of MetS is complex.Studies have suggested that insulin resistance,obesity,low-grade inflammation,oxidative stress,and endothelial functional impairment are all associated with the development of MetS.As important regulators of lipid and glucose metabolism and insulin sensitivity,protein disulfide isomerase(PDI)family have received increasing attentions.ERp57 protein,a member of the PDI family,it plays a variety of functions in different positions of different cells.Moreover,a large number of studies have shown that ERp57 dysfunction is associated with the pathological processes of many diseases,including cardiovascular disease,metabolic disease,neurodegenerative disease and tumor.Therefore,we suggest that ERp57 is closely related to the pathological processes,such as lipid metabolism and glucose metabolism in vivo.Currently,lifestyle improvement is the basic intervention for the treatment of MetS.When lifestyle interventions are not sufficient,hypoglycemic,lipid-lowering,and anti-hypertensive drugs can be chosen to treat MetS.However,for patients with different genetic backgrounds,the same treatment regimen tends to achieve varied treatment effects.It has been envisioned for a long time that genetics could drive the development of individualized drugs by identifying subgroups of patients most likely to respond.However,there are still no targeted drugs for the treatment of MetS.Therefore,there is an urgent need to develop new ideas in gene-directed therapy for MetS patients.Single nucleotide polymorphism(SNP)research has become a more popular method for the study of MetS pathogenic genes with the advantages of large number,high distribution density,stable genetic characteristics and convenient genotyping methods.There is a lack of studies between ERp57 gene polymorphism and MetS.We explored the relationship between ERp57 gene SNP locus rs2788 polymorphism and MetS in both case-control and follow-up studies.In addition,we explored whether the ERp57 gene polymorphism can be used to treat MetS patients in terms of both drug sensitivity and lifestyle interventions,thus providing individualized treatment guidance.Objectives1.Analysis of the relationship between the ERp57 gene SNP locus rs2788 polymorphism and MetS susceptibility in a Han Chinese population in Shandong,China;2.Analysis of the relationship between the ERp57 gene SNP locus rs2788 polymorphism and longitudinal changes in MetS and its components during follow-up;3.To explore whether the ERp57 gene polymorphism can be used to treat MetS patients in terms of both drug sensitivity and lifestyle interventions,thus providing individualized treatment guidance.Study methodsBy random sampling,Chinese Han population living in Jinan,Shandong Province was recruited from January 2007 to December 2007 and with a follow-up from 2007 to 2012.The data collection consisted of three parts:questionnaire,physical examination,and blood sample collection.In addition,the ERp57 gene SNP locus rs2788 genotype was examined using the Sequenom MassArray genotyping system.SPSS was used to analyze data.Results1.The minor allele frequency(MAF)was 0.344 for rs2788.Genotype distribution in total,MetS and control subjects were in Hardy-Weinberg equilibrium,respectively.Participants were age-and gender-matched in Control and MetS groups.Compared with the Control group,BMI,WC,SBP,DBP,TG,TC,LDL-C,FPG and alcohol consumption rate of MetS group were significantly increased,HDL-C and smoking rate of MetS group were significantly decreased.2.We divided the overall population into normal and abnormal groups of WC,BP,TG,HDL-C and FPG according to the diagnostic criteria of MetS.Carriers of G allele as compared to A allele had increased susceptibility to MetS with significantly increased WC,BP,and TG.3.G allele was shown to be an independent risk factor for MetS.GG genotype was indicated to be an independent determinant for an increase of WC in codominant model.4.We found that the number of MetS’ risk factors significantly reduced in the population who implemented weight control,diet control and physical exercise.Carriers of A allele had benefit significantly from weight control,diet control and physical exercise with the number of MetS’ risk factors significantly reducing.On the contrary,for carriers of G allele,physical exercise did not affect the number of MetS’risk factors.5.G allele was demonstrated to be an independent contributor to the longitudinal aggravation of HDL-C and FPG.6.After the ACEI or ARB medicines treatment,carriers of A allele exprienced a significant drop in DBP.Conclusions1.G allele carriers in the ERp57 SNP locus rs2788 were MetS susceptible and at a higher risk to abdominal obesity,hypertriglyceridemia,and elevated blood pressure;2.G allele carriers in the ERp57 SNP locus rs2788 is an independent risk factor for MetS through increased WC;3.During the development of MetS,HDL-C and FPG did not improve significantly in G allele carriers in the ERp57 SNP locus rs2788,4.G allele carriers in the ERp57 SNP locus rs2788 failed to significantly improve MetS progression through physical exercise;5.G allele carriers in the ERp57 SNP locus rs2788 taking ARB or ACEI antihypertensive drugs had poor blood pressure lowering.