Study On The Association Between Diabetic Microangiopathy And Polymorphisms Of The Aldose Reductase Gene In Type 2 Diabetes Mellitus

ObjectiveAldose Reductase,the rate-limiting enzyme of the polyol pathway,has been considered to be closely associated with diabetic microangiopathy.high levels of intracellular glucose may increase AR activity and gene expression.Our research is to investigate the relationship between polymorphisms of AR gene and diabetic microangiopathy(DIMP) in Chinse type 2 diabetes. MethodsA case-control study for 421 Chinese subjects (including 320 type 2 diabetes mellitus with or without nephropathy or retinopathy and 99 non-diabetes control) was performed. The number of (AC)n dinucleotide of AR gene was determined by PCR-denaturing polyacrylamide gel electrophoresis,and PCR-RFLP techniques were performed to screen the polymorphisms of C(-106)T at S'-regulatory region of AR gene.The diffrence of frequency in alleles and genotypes were compaired among groups. Results(1) Tandem (AC)n repeats of the AR gene were highly polymorphic and 10 alleles (Z-10~Z+8),28 genotypes were observed in type 2 diabetes mellitus and controls. The most prevalent allele was 24 times in (AC)n repeat which was designated as Z allele.(2) A polymorphism C(-106)T was discovered both in type 2 diabetes mellitus and controls,and no diffrence among two groups for the frequency of C allele, T allele,and the C/C,C/T,T/T genotypes.(3) In type 2 diabetes mellitus with nephropathy or retinopathy, a increased frequency of Z-2 allele was found in comparison with type 2 diabetes mellitus without microangiopathy .(4) an elevated frequency of Z-2 allele was observed in type2 diabetes mellitus with early-srage nephropathy (microalbuminuria and clinical proteinuria) as compared with type 2 diabetes mellitus without nephropathy ,and the same result found in type 2 diabetes mellitus with preproliferative retinopathy or proliferative retinopathy. (5) there was no difference of T allele frequency among stages of diabetic nephropathy groups or diabetic retinopathy groups,and it was significantly higher in these groups than diabetes mellitus without complications.(6) the haplotype carrying both risk alleles Z/T was increased in type 2 diabetes mellitus with nephropathy or retinopathy compaired with none-complications . Conclusion1. There are 10 alleles (Z-10~Z+8),28 genotypes of (AC)n repeats in the AR gene in Chinese people.2. AR gene alleles are associated with the susceptibility of diabetic microangiopathy. The Z-2 allele of the AR gene may be a risk factor for early-stage nephropathy in type 2 diabetes mellitus,whereas, it may be a risk for the development and progression of diabetic retinopathy in Chinese subjects.3. The C(-106)T polymorphism at 5'-regulatory region of AR gene contrbutes to the development and progression of diabetic nephropathy or retinopathy in type 2 diabetes mellitus4. (AC)n dinucleotide of AR gene was assosiated with C(-106)T.More studies are now reququeired to confirm whether the two polymorphisms has a linkage disequilibrium...