| Objective: Diabetes mellitus is a disease characterized by high blood glucose and it can cause abnormalities in the functions and the structures of various organs and tissues. Type 2 diabetes is the predominant form of diabetes accounting for 90% of all diabetes cases. With the economic development and improvement of life standard, the morbidity of diabetes mellitus is increasing. The vascular complications are the major causes of morbidity and mortality in the diabetic patients. Without its vascular complications, Type 2 diabetes wouldn't be the world's most important public health problem.The key to conquering diabetes mellitus is to understand its etiology. Heredity plays an important role in the development of Type 2 diabetes mellitus. The β3 adrenergic receptor is identified as the third subtype of adrenoreceptor after β1 and β2 recently, it is found to be involved in activating lipolysis and energy expenditure. A T→C missense mutation in the 190 locus of β3-adrenergic receptor gene results in the replacement of the 64 tryptophan by arginine forming the Trp64Arg allele.The mutation can impair the receptor activity resuling in the decrease of its lipolytic function and thermogenesis and tendency to develop abdominal obesity which is a good indicator of insulin resistance. β3-adrenergic receptor gene polymorphism has been showed to be associated with obesity and insulin resistance.Obesity is the independent risk factor of Type 2 diabetes mellitus while IR is one of the primary pathogenesis of type 2 diabetes mellitus.In this study, we examined the β3-AR genepolymorphism among type 2 diabetics with microvascular complications and peripheral neuropathy in order to determine whether the P" 3-AR gene is the risk gene of diabetes and its microvascular complications and neuropathy and to explore the molecular mechanisms of type 2 diabetes mellitus.A new effective target is expected to find for prevention and treatment of diabetes and its complications.Methods:The research design was a case-control study. 180 cases of Chinese Shandong Han Type 2 diabetics who were diagnosed according to 1998 WHO criteria were selected into the study.Of the patiens, 50 were diabetics without any complications,52 with diabetic nephropathy(DN),47 with diabetic retinopathy(DR), 31 with diabetic neuropathy(DPN)and 54 health controls. The clinical and biochemical data of all subjects were recorded and determined including blood pressure,height,weight,waist circumstance,hip girth,body mass index(BMI),waist hip ratio(WHR), fasting plasma glucose(FBG),total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL-c),urea nitrogen(BUN),blood creatinine,(Cr), hemoglobin(HbAlc),fasting insulin etc. Genomic DNA was extracted from peripheral blood, The single nucleotide polymorphism (SNP) frenquencies of P 3-AR gene were detected in the diabetic patients and health controls using polymerase chain reaction-restrictive fragment length polymorphism assay (PCR-RFLP). The normal distribution data was described by MeandrSD, and the ANOVA was employed to compare the differences between groups. Bias-distribution data was transformed to the normal distribution data and then compare Chi-square was employed to test the difference of frequencies. Logistic regression was employed to analyse the risk factors.All the statistics were performed with the software of SPSS 11.5 for windows.Results: The distribution of P" 3-AR gene polymorphism is associated with ethnicity and region. The P 3-AR gene polymorphism distribution in the Chinese Shandong Han population was different frompopulations of other ethnicities and in other regions.The Trp64Arg genotype was distributed in the normal weight group,over weight group and obesity group.In the health group,BMI and WHR in the Arg64 carriers were higher than those with the wild genotype(P<0.05). There was no significant difference in the insulin resistance index(HOMA-IR). In the diabetic patients WHR and HOMA-IR of the Arg64 carriers were significantly higher than those with the wild genotype(P<0.05),BMI of female Arg64 carriers were higher than that of wild type(P<0.05),there was no significant difference in male patiens.There was significant difference of the genotype and allele frequencies between the overweight/obesity group and normal weight group. There was no significant difference of the distribution of genotype and allele frequencies between the health controls,diabetics without any complications and diabetic retinopathy and diabetic neuropathy(P>0.05) suggestting that P 3-AR gene mutation was not associated with diabetic retinopathy and diabetic neuropathy. . The frequency of Arg64 allele of diabetic nephropathy was significantly different from controls, diabetics without any complications(P<0.05) suggestting that the mutation was associated with diabetic nephropathy. High blood pressure ,HbAlc, duration of disease ,HOMA-IR were the risk factors for diabetic nephropathy .HbAlc,duration of disease,HOMA-IR were risk factors for diabetic retinopathy and diabetic neuropathy..Conclusion:!. The distribution of ￡ 3-AR gene polymorphism is accociated with ethnicity and region. The P 3-AR gene polymorphism distribution in the Chinese Han population was different from populations of other ethnicities. In the Chinese Shandong Han population there was no significant difference of the 3 3-AR genotype and allele frequencies between the health controls and Type 2diabetics.2. In the health controls and diabetic patients the WHR of Arg64 carriers were higher than those of the wild type(P<0.05). The frequenciesof 3 3-AR phenotypes and alleles in over-weight/obesity group were significantly higher than in the normal group. In the diabetic patients the BMI of women with the 3 3-AR gene Trp64Arg mutation was significant higher than women without the mutation,but not in men suggestting that 3 3-AR gene polymorphism is associated with obesity,especially abdominal obesity, and this association is related to sex.Our finding suggest that the 3 3-AR gene polymorphism may play a role in the occurrence and development of obesity.3.In type 2 diabetes,the HOMA-IR values of those with 3 3-AR mutation were higher than those without the mutation suggestting that there is an association between the Trp64Arg mutation of 3 3-AR gene and insulin resistance.4.There were no significant difference of the 3 3-AR genotype and allele freqencies among diabetic retinopathy and diabetic neuropathy , type 2 diabetes without any complications and controls.There was significant difference of the 3 3-AR genotype and allele freqencies among the diabetic nephropathy group and type 2 diabetes without any complications group and controls suggestting that 3 3-AR Arg64 gene is not associated with diabetic retinopathy and diabetic neuropathy but is associated with diabetic nephropathy.5. Type 2 diabetes mellitus and diabetic micorvascular complations are related to polygene and environmental factors.The effect of 3 3-AR gene may be modified or weaken by many factors above. In conclusion the 3 3-AR gene may not be a major determinant of type 2 diabetes.6.It is suggested that 3 3-AR gene is one of the susceptible genes of obesity and insulin resistance in Shandong Han population.In this study we analysed the role that 3 3-AR gene may play in the diabetic microvascular complations and diabetic neuropathy and provided useful data for exploring the molecular genetic mechanisms of diabetic vascular complications and diabetic neuropathy.
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