Study On The Relationship Between The Polymorphisms Of Betacellulin Gene And Type 2 Diabetes Mellitus And Its Insulin Secretion

Objectives Betacellulin which has been found to be a new member of the epidermal growth factor (EGF) family appears in early pancreatic development and expresses mainly in human pancreas. It palys an important role in regeneration of pancreatic P-cell and pancreatic islet. A mutation in the betacellulin gene could potentially result in a decreased number of or abnormally functioning 6-cells and thereby contribute to the development of type 2 diabetes. Our research object is the Han nationality population in Tianjin for a long time. There are 211 type 2 diabetes patients and 102 healthy control subjects in this study. The aim of this study is to investigate the prevalence of the T19G polymorphism of BTC extron 1 by PCR-RFLP technique. In addition, another aim is to find out the correlation between the polymorphism type 2 diabetes and its insulin secretion in the Han nationality population in Tianjin of China. Methods1. To collect the blood samples of type 2 diabetes patients and healthy control subjects.2. To extract and to purify the genomic DNA from the collected bloodsamples.3. Using PCR-RFLP technique, the T19G polymorphism site of BTC extron 1 was screened in 211 type 2 diabetes patients and 102 healthy controls.4. To sequence the polymorphic gene found by RFLP technique.5. To analyse the clinical data.Results (1) To the T19G polymorphism site of BTC extron 1, 209(99.05%) with TT genotype and 2(0.95%) with TG genotype were found in 211 diabetes subject. The G allele frequency is 0.47% in diabetes subjects. While 90(88.2%) with the TT genotype and 12(11.8%) with TG genotype were found in 122 healthy control subjects. The G allele frequency is 5.88% in control subjects. The GG genotypes is absent in two groups. The frequency of TG genotype and G allele are higher in control subjects than diabetes subjects (PO.001). (2)The secretion index of pancreatic P-cell with TG genotype is lower than TT genotype in diabetes subjects (PO.05) . However The secretion index of pancreatic P-cell with TG genotype is higher than TT genotype in control subjects (PO.05) . (3)We compared some metabolic indexes between TT genotype and TG genotype subjects, and there is no significant differences in BMI, SBP, DBP, P2PG, TG, CHO, LDL-c and HDL-c. FPG of TT genotype subjects is lower than TG genotype subjects (P<0.05) . (4)The frequency of G allele among Chinese is lower than Caucasian (^'=50.483, PO.001) , African-American (/'=151.372, PO.001 ) in diabetes subjects and the difference is significative. The frequency of G allele among Chinese is lower than JapaneseC t&IE /'=2.155, P>0.05 ),but the difference is not significative. The frequency of G allele among Chinese is lower than Caucasian (.x* =11.122, P=0.001) , African-American (*'=89.691, PO.001) and Japanese(x '=6. 757, R0. 01) in control subjects.Conclusions In the Han nationality population in Tianjin of China, the T19G polymorphism of BTC extron 1 is associated with diabetes and its insulin secretion. The GG genotypes play a protective role in the development of type 2 diabetes.