Research On The Effect Of AMPK A₂ Gene On Type 2 Diabetes And Adiponectin

Objective We examined the distribution of Single nucleotide polymorphisms(SNPs) rs2143754 of amp-activated protein kinase(AMPK) gene among Tianjin Hanpopulation with type 2 diabetes(DM) and nomal population,in order to investigate theassociation between the polymorphism of human AMPKa₂ gene and type 2 diabetescomplication, insulin resistance and Adiponectin.Methods 80 normal subjects and 300 type 2 diabetics were included in thisstudy. Fasting blood was collected,Genomic DNA was isolated from peripheral bloodleucocyte according to protease K method.By means of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and sequencing, thepolymorphism of AMPK-rs2143754 G/T were determined.Applying the methods ofELISA to examine the level of Adiponectin.Results (1)There was polymorphism of AMPK-rs2143754 in both type 2diabetics and normal subjects.The distribution of AMPK-rs2143754 T/T,G/T andG/G genotypes:DM group was37%, 52%, 11%,respectively, T allele frequency was63%;control group was 24%, 44%, 32%,respectively, T allele frequency was54%;There was significant difference of genotype constituent ratio (P=0.017).(2)There was significant association between the polymorphism of AMPK-rs2143754 and insulin resistance in type 2 diabetics.AMPK-rs2143754 T/T genotypehad lower FINS and P₂INS,higher HOMA-IR than G/T and G/G genotype,(P＜0.01).(3)There was association between the polymorphism of AMPK-rs2143754 anddyslipidemia in type 2 diabetics. AMPK-rs2143754 T/T genotype had higher TC,TG,LDL-C, and lower HDL than G/T and G/G genotypes,(P＜0.05).(4)There wassignificant association between the polymorphism of AMPK-rs2143754 and diabeticcardiovascular complication(P＜0.01).AMPK-rs2143754 T allele was independent risk factor for diabetic cardiovascular complication.(5)There was significantassociation between the polymorphism of AMPK-rs2143754 and adiponectin(P＜0.01),the T/T genotype had much lower level of adiponectin.Both patients withdiabetic cardiovascular complication and low-limb arterial occlusion had loweradiponetin.It was demonstrated that adiponetin was relevant with diabeticmacroangiopathy, as well as the hypertension(P＜0.01).Adiponectin increased alongwith diabetic nephropathy aggravating(P＜0.01).(6)There was no significantassociation between the polymorphism of AMPK-rs2143754 and diabeticmicroangiopathy.Conclusion (1)The polymorphism of AMPK-rs2143754 G/T existed amongTianjin Han population,and it was revelant with T2DM,AMPK-rs2143754 T/Tgenotype had higher FPG,P2PG,higher insulin and lipid level,which the insulinresistance was aggravated,and the ratio of cardiovascular complication wassignificant decreased. It was presumed that T allele maybe the risk gene,G allelemaybe the protecting gene.(2)There was significant association between thepolymorphism of AMPK-rs2143754 and adiponectin,T/T genotype had much loweradiponectin.Adiponectin is negative correlation with HOMA-IR.Adiponectin indiabetic macroangiopathy was lower than non diabetic macroangiopathy, it wasdemonstrated that adiponectin has antiatherogenesis effect.Adiponectin increasedalong with diabetic nephropathy aggravating. Adiponectin took part in the onset ofhypertension, the higher the blood pressure,the lower adiponectin.