Study On The Correlation Between Genetic Polymorphism And Type 2 Diabetes And Its Metabolic Indicators In The Middle-aged And Elderly Population In China

Objective:To explore the relationship between 9 gene single nucleotide polymorphisms(SNPs)and middle and old type 2 diabetes in Chinese population,including solute carrier family 30/zinc transporter,member 8(SLC30A8)(rs13266634 and rs3802177),protein tyrosine phosphatase receptor type D(PTPRD)(rsl 7584499),high mobility group AT-hook(HMGA1)(rs139876191),et al.Methods:A total of 1781 type 2 diabetic patients(the diabetes group)and 2506 healthy controls(the control group)from Nanjing City,China,were included in this case-control study.Then genotypes of nine target loci including gene SLC30A8(rs3802177 and rsl3266634),PTPRD(rs17584499),PCSK1(rs6235),PEX5L(rs7630877),PPP2R2C(rs3796398),KIAA1530(rs2276904),CENTD2(rs11603334)and HMGA1(rs139876191)were detected.The relation between type 2 diabetes and these gene polymorphisms was analysed using Binary Logistic Regression.The risk was presented as OR value.Results:1.The male percentage,age and body mass index(BMI)levels of the diabetes group were higher than those of the control group(P<0.001).Compared with normal controls,diabetes patients had elevated triglycerides and lower high-density lipoprotein cholesterol(P<0.001).2.SLC30A8 gene rs13266634 and rs3802177 were associated with type 2 diabetes.The risk of type 2 diabetes of C allele carriers was 1.148 times(OR=1.148,P=0.005)and 1.123 times(OR=1.123,P=0.018)that of T allele,respectively.3.It showed statistical correlation between HMGA1(rsl39876191)and type 2 diabetes(P=0.042).After correction of gender,age,body mass index,the statistical difference was more significant between two groups(OR = 1.286,P = 0.004).4.CENTD2(rs11603334)gene polymorphism was also associated with type 2 diabetes under the dominant genetic model(P=0.002).Conclusion:1.The polymorphisms of rs13266634 and rs3802177 in SLC30A8 gene are associated with middle and old type 2 diabetes in Chinese population.The C allele might be a risk allele of T2DM.2.HMGA1 rs139876191 and CENTD2 rs11603334 gene polymorphisms under the dominant gene model were correlated with type 2 diabetes in population of this study.Objective:To explore the relationship between 9 gene single nucleotide polymorphisms(SNPs)and metabolic traits in middle and old normal Chinese population,including parameters of glucose,insulin sensitivity,beta-cell function and serum lipid levels.Methods:The normal controls who had participated in the above case-control study were included in this research,2506 samples in all.The oral glucose tolerance test and insulin releasing test was performed on each subject.Then several metabolic traits were derived from their laboratory test results.Meanwhile,genotypes of nine target loci including gene SLC30A8(rs3802177 and rs13266634),PTPRD(rs17584499),PCSK1(rs6235),PEX5L(rs7630877),PPP2R2C(rs3796398),KIAA1530(rs2276904),CENTD2(rs11603334)and HMGA1(rsl39876191)were detected.The linear regression analysis was applied to assess the relation between gene SNPs and these metabolic traits.Results:1.SLC30A8 gene was associated with increased fasting and 30 minutes plasma glucose during OGTT and elevated HbAlc level.We observed decreased CIR and DI for the C allele(CIR/DI,P=0.003/0.001),thus reduced beta-cell function.2.SNP of rs11603334 in CENTD2 was related to decreased fasting serum insulin level(P=-0.004,P=0.026)and lower HOMA-IR(?-0.043,P=0.029).In addition,it was found to be also associated with reduced beta-cell function,with a regression coefficient of-0.042 in HOMA-?(P=0.035).3.The HMGA1 gene variant was associated with reduced BIGTT-SI level(?=-0.036,P=0.04),and with elevated HDL-C under the recessive model(P=0.038).4.As to lipid,rs6235 in PCSK1 was related with reduction of TC(P=0.009)and LDL-C levels(P=0.024),rs7630877 in PEX5L with decreased HDL-C level(P=0.029),under the recessive model.Conclusion:1.The polymorphisms of rs 13266634 and rs3802177 in SLC30A8 gene are associated with increased plasma glucose and reduced beta-cell function in middle and old normal Chinese from Nanjing area.2.CENTD gene(rs17584499)and HMGA1 gene(rs139876191)are related with insulin resistance,insulin sensitivity and beta-cell function of this study subjects.3.Under the recessive model,gene SNPs of HMGA1,PCSK1 and PEX5L are associated with alteration of lipid levels in this population.