Study On The Relationship Between Chymase Gene Polymorphism And Type 2 Diabetic Complications

ObjectivesChymase, the rate-limiting enzyme of the RAS system, has been considered to be closely associated with the cardiac-vascular disease as well as hypertension, cardiac hypertrophy, congestive heart failure and atherosclerosis, and diabetic complication.Clinical research was implicated that the strict control of blood glucose could be prolonged and lightened the occurance and progression in type 2 diabetes patients, but could be not completely prevented it' s onset. On the other hand,plasma angiotensin converting enzyme activity between the diabetic nephropathy group and non-nephropathy group was not revealed the marked difference, but the plasma concentration of angiotensin II was still high, also angiotensin converting enzyme inhibitor therapy could not completely prevent the progression of diabetic complication as well as diabetic hypertension.Thus,there be suggested that diabetic complication were involved with angiotensin II-forming pathway and other factors, and chymase play a role in the onset of vascular disease.We investigated the profound involvement between chymase gene polymorphism and diabetic vascular complication in Chinese type 2 diabetes patients, and analysed simultaneously the correlation between chymase and angiotensin converting enzyme gene polymorphism. Material and MethodsAccording to the diagnostic criteria of WHO in 1999, 405 non-related diabetes were randomly recruited, as well as 169 non-related and non-diabetes control subjects enrolled.(1) The clinical and biochemical indexes were collected.(2) Total genomic DNA is extracted conventionally in peripheral blood leucocytes from all the participant and purified genome DNA by using digestion-lysis method with protease K.(3) The polymorphism of ACE I/D at intron 6 and CMA A/G genotype at position-1903 of 5' untranscribed region were determined by using PCR and RFLP in 405 unrelated patients with type 2 diatetes and 169 randomly selected healthy control subjects.(4) Direct sequencing of the representative PCR products with variant patterns.(5) One Way ANOVA analysis t-test x2-test and multiple logistic regression analysis(Backward LR) were performed by using SPSS 12.0 to analysis the result.Results(l)No differences in the genotype distributions or allele frequenc ies of Chymase and Angiotensin converting enzyme gene between the controls and diabetic group were observed.(2)The genotype distributions or allele frequencies of Chymase were relevant differences in non-diabetic nephropathy, early diabetic nephropathy and overt diabetic nephropathy groups than control (P<0.05); the CMA AG genotype frequencies of early diabetic nephro pathy and overt diabetic nephropathy groups were higher than control, but the difference was not statistically signifleant(P>0. 05);however, there were higher than non-diabetic nephropathy group (P<0. 05).No differences in the genotype distributions or allele frequencies of angiotensin converting ezyme were observed(P>0.05).The genotype distributions or allele frequencies of Chymase and angiotensin converting ezyme were no differences in non-diabetic retinopathy, background diabetic retinopathy and proliferative diabetic retinopathy groups than control(P>0. 05).Diabetic nephropathy and retinopathy were also analyzed jointly with the genotype distributions or allele frequencies of Chymase angiotensin converting ezyme, where these were found to have significant differences among DN-/DR-, DN+/DR-, DN-/DR+, DN+/DR+ and control groups.(3) The genotype distributions or allele frequencies of Chymase angiotensin converting ezyme were "significantly differences between control and subgroups in type 2 dibetic patients with diabetic macro angiopathy ,lower extremitas vascular disease and hypertension (P<0.05). Diabetic lower extremitas vascular disease and hypertension were also analyzed jointly with the genotype distributions or allele frequencies of Chymase angiotensin converting ezyme, where these were found to have more significant differences among all groups.The frequences of chymase...