Relationship Between ABCC8 And WFS1 Genes With Type 2 Diabetes In Chinese Han Individuals

Objective:To explore the association of SNPs in ABCC8 and WFS1 with beta cell function as well as insulin sensitivity in Tianjin Han population.Methods:We screened the objects with type 2 diabetes(T2DM),with impaired glucose regulation(IGR)and normal controls(NGT).560 individuals underwent an OGTT with measurements of glucose and insulin concentrations at 0,30,60,120,180min of OGTT.We collected some biochemistry parameters.After an overnight fasting,all subjects' venous blood was drawn for DNA extraction.Using PCR-RFLP we detected the ABCC8 rs 1799859 G/A and WFS1 rs6446482 C/G polymorphism in all subjects.We sequenced the genes.Insulin resistance was estimated according to the homeostasis model assessment insulin resistance index(HOMA-IR)and insulin sensitive index(ISI).beta cell function was measured according to HOMA-??insulin 30 min-fasting insulin/glucose 30min(?I30/?G30)and area under curve of insulin(AUCI).We analyzed the clinical data in SPSS 17.0 software.Results:(1)There was no significant difference for age and BMI in the NGT?IGR and T2DM groups.The blood pressure(SBP?DBP)?plasma glucose(FPG?P2BG)?HbA1c and blood lipids(TG?TC?LDL)in T2DM group were higher than NGT group,the difference had statistic value(P<0.05);P2BG and TG in IGR group were higher than NGT group,the difference had statistic value(P<0.05).FPG?P2BG and HbA1c in T2DM group were higher than IGR group,the difference had statistic value(P<0.05).(2)HOMA-???I30/?G30 and AUCI decreased gradually in the NGT?IGR and T2DM groups,HOMA-IR increased and ISI decreased gradually in the three groups,the difference had statistic value(P<0.05).(3)In this study,we confirmed that ABCC8 rs1799859 had three genotypes in each group.The frequency of risk allele A/A homozygote and risk allele A in T2DM group was significantly higher than in NGT group(P<0.05).The diabetes risk for ABCC8 rs1799859 A allele carrier was 2.2 fold higher than the G allele carrier.HOMA-???I30/?G30 was lower in A/A than G/G,the difference had statistic value(P<0.05).(4)We found that WFS1 rs6446482 had three genotypes.The frequency of allele C was respectively 15%?11.7%?10%in NGT group?IGR group and T2DM group,there was no significant difference among the three groups.There was no significant difference in C/C?C/G and G/G genotypes in HOMA-???I30/?G30?HOMA-IR and ISI.Conclusion:(1)ABCC8 rs1799859 G/A and WFS1 rs6446482 G/C mutation existed in Tianjin Han population.(2)Frequency of risk allele A in T2DM group was significantly higher than in NGT group.The diabetes risk for ABCC8 rs 1799859 A allele carrier higher than the G allele carrier.The polymorphism of rs 1799859 genes were closely associated with impaired beta cell function,the decrease of insulin secretion,which was not associated with insulin resistance and insulin sensitivity.We confirmed that ABCC8 gene was the diabete's susceptibility gene.(3)The frequency of WFS1 rs6446482 genotypes was no significant difference in the NGT?IGR and T2DM groups.The polymorphism of rs6446482 genes may be not associated with T2DM in Tianjin Han population.(4)ABCC8 variations?SBP?TC and TG were the risk factors for diabetes,while HOMA-? and ?G30 was the protective factor.