Relationship Between SLC30A8 And PTP1B Genes With Type 2 Diabetes In Chinese Han Individuals

Objective:To explore the association of SNPs in SLC30A8 rs11558471 and PTP1B rs754118 with beta cell function,insulin resistance and type 2 diabetes.Methods:Applying OGTT tests,We screened 300 cases of type 2 diabetes,200 cases of impaired glucose regulation and 100 cases of normal glucose tolerance whose age and sex matched in Tianjin.Collection of fasting blood samples,the whole blood is used to extract genomic DNA,the serum is used for the detection of biochemical indicators.Using PCR-RFLP,we detected the SLC30A8 rs11558471 and PTP1B rs754118 polymorphism in all subjects.We sequenced the target genes.Insulin resistance was estimated according to the homeostasis model assessment insulin resistance index(HOMA-IR),beta cell function was measured according to HOMA-β,insulin 30 min—fasting insulin/glucose 30 min(△I30/△G30).We analysed the clinical data using the SPSS 13.0.Results:(1)The gender,age,and body mass indices are no significant differences among normal glucose tolerance(NGT),impaired glucose regulation group(IGR)and type 2 diabetes(T2DM)(P>0.05),baseline levels were comparable.The systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),postprandial blood glucose two hours(P2BG),glycosylated hemoglobin(HbAlc),triglycerides(TG),serum total cholesterol(TC)and Low-density lipoprotein cholesterol(LDL)of T2DM group were higher than that of NGT group,the difference was statistically significant(P<0.05).Two-hour postprandial blood glucose(P2BG)and triglyceride(TG)of IGR group were higher than that of NGT,the difference was statistically significant(P<0.05).(2)The insulin resistance index(HOMA-IR)gradually increased and insulin sensitivity index(ISI)decreased gradually in the three groups,the difference was statistically significant(P<0.05).(3)We found that the SLC30A8 rs11558471 gene polymorphism exits in NGT,IGR and T2DM groups.The genotype frequencies of A/A,G/A,G/G were 23.0%,33.0%,44.0%in NGT group;24.0%,40.0%,36.0%in IGR group;38.7%,36.7%,24.6%in T2DM groups respectively.Risk allele A frequency was 39.5%in NGT group,44.0%in IGR group,57.0%in T2DM group.The frequency of risk allele A/A homozygote and risk allele C in T2DM group significantly higher than that of normal glucose tolerance group(P<0.05).The diabetes risk for A allele carrier was 2.00 fold higher than the G allele carrier.Fasting C-peptide,120 minutes C-peptide,pancreatic B cell function index(HOMA-B),early of β cell function index(△I30/△G30),early glucose disposition index(DI30),the glucose disposition index(DI-HOMA)in the G/G,G/A,A/A genotype group decreased gradually(P<0.05).(4)We found that PTP1B rs754118 had C/C,T/C,T/T genotypes among three groups.The genotype frequencies of C/C,T/C,T/T were 21.0%,32.0%,47.0%in NGT group;22.0%,39.5%,38.5%in IGRgroup;and 39.3%,34.0%,26.7%in T2DM group respectively.The frequency of risk allele C was 37.0%in NGT group,41.8%in IGR group,and 56.3%in T2DM group.The frequency of risk allele C/C homozygote was 39.3%,and the frequency of risk allele C was 56.3%in T2DM group,which was significantly higher than that of NCT group(P<0.05).The diabetes risk for C allele carrier was 2.19 fold higher than the T allele carrier.Fasting insulin,fasting C-peptide,the two-hour postprandial C-peptide,HOMA-B,△I30/△G30,DI-HOMA,DI30 and ISI gradually decreased in the T/T,T/C and C/C genotype,which were significantly different between T/T and C/C type,the difference was statistically significant(P<0.05),Conclusion:(1)SLC30A8 rs11558471 and PTP1B rs754118 gene polymorphism existed in Tianjin Han population.(2)The polymorphism of SLC30A8 genes were closely associated with impaired beta cell function,the decrease of insulin secretion,which was not associated with insulin resistance and insulin sensitivity.The polymorphism of PTP1B genes were closely associated with impaired beta cell function,the decrease of insulin secretion,insulin resistance and insulin sensitivity.We confirmed that SLC30A8 and PTP1B genes were the diabetes susceptibility genes.(3)SLC30A8 G/A and PTP1B T/C variations,TG,SBP and Body mass index(BMI)were the risk factors for diabetes,while HOMA-B was the protective factor.