The Study Of The Correlation Among β₃-AR Gene Polymorphism, Serum Adiponectin Levels And Type 2 Diabetic Nephropathy

Objective: To investigate the relationship amongβ₃ adrenergic receptor (β₃-AR) gene polymorphism ,serum adiponectin levels and the type 2 diabetic nephropathy.Method: ninety patients with type 2 diabetes mellitus were recruited in the study. They all were in-patients from Yishui Centeral Hospital, aged from 43 to 72, complied with 1999 WHO diagnostic classification standard. According to UAER, these patients were devided into three groups: simple diabetes mellitus group (SDM,n=32);early diabetic nephropathy group(EDN, n=28); clinical diabetic nephropathy group(CDN,n=30).pYAR gene was detected in both diabetic patients and health controls by polymerase chain reaction-restrictive fragment length polymorphism assay (PCR-RFLP), Enzyme-linked immunosor-bent assay(ELISA) was applied to measuring serum level of adiponectin (APN),BMI,Blood pressure,HbA1c ,FPG ,CH (cholesterol) ,TG (triglyeeride).. ,inslulin and urine albumen were determined simultaneously.Results :The distribution ofβ₃-AR gene polymorphism was associated with ethnicity and region. The frequency of Arg64 allele in Shandong Linyi Han population was significantly lower than that in Pima Indians (P<0.05), slightly lower than that in Japanese, and slightly higher than that in Finns. There was no significant difference of the Arg64 allele frequencies between the diabetes' group and control group (P>0.05) ,and there was significant difference between the simple diabetes mellitus group and diabetic nephropathy group (P<0.05) ,but there was no significant difference between the early diabetic nephropathy group and clinical diabetic nephropathy group (P> 0.05) .There was significant difference of the Arg64 allele frequencies between the normal weight group and over weight group,obesity group (P<0.05) .The Arg64 allele frequencies in relative insulin sensitive group(24%) was significant higher than that in insulin resistant group (14%).BMI and WHR in the Arg64 carriers In control group were higher than those with the wild genotype (P<0.05), BMIand HOMA-IR of the Arg64 carriers In the diabetes groups were significantly higher than those with the wild genotype (P<0.05) .The level of serum adiponectin in control group was significantly higher than that in diabetes groups(P<0.01), The level of serum adiponectin was higher in early diabetic nephropathy group compared with simple diabetes mellitus group (P<0.01) ,and was higher in clinical diabetic nephropathy group compared with early diabetic nephropathy group (P<0.01) .Person correlative analyses showed serum adiponectin to be positively associated with UAER (r=0.348)and to be negatively associated with BMI and HOMA-IR (r1=-0.375 , r2=-0.368). Logistci regression analyses showed that high blood pressure, HbA1c, duration of disease were the risk factors for diabetic nephropathy.Conclusion: The distribution ofβ₃-AR gene polymorphism is accociated with ethnicity and region. In Chinese Shandong Linyi Han population,there was no significant difference of theβ₃-AR gene alleles frequencies between the health controls and Type 2 diabetics. The frequencies ofβ₃-AR alleles in diabetic nephropathy group were significantly higher compared with the simple diabetes mellitus group, but there was no relationship between the the frequencies ofβ₃-AR alleles and the stages of DN,which suggested thatβ₃-AR Arg64 allele gene may be a risk gene in DN,butβ₃-AR Arg64 allele gene may not be a major determinant of DN.the Trp64Arg mutation ofβ₃-AR gene was associated with obesity and insulin resistance.The level of serum adiponectin in health controls was significantly higher than that in the Type 2 diabetics. The serum adiponectin level was increased gradually with the progression of DN. The level of serum adiponectin was increased gradually with the injure degree of the nephropathy. The level of serum adiponectin was positively associated with UAER and was negatively associated with BMI and HOMA-IR.